Pharmacia

Pharmacia

Published by Pensoft Publishers and Bulgarian Pharmaceutical Science Society

Online ISSN: 2603-557X

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Print ISSN: 0428-0296

Disciplines: Pharmacology & Pharmacy

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324 reads in the past 30 days

Via mTOR-dependent HIF-1 alfa activation, GLP-1R signaling impacts glucose metabolism in beta cells. When GLP-1 binds with its receptor GLP-1R (G-protein receptor), adenylyl cyclase (AC) is activated. The cyclic ATP is increased, which promotes the mTOR pathway in beta cells, HIF-1 alfa upregulates the transcription of glycolic genes. The increased glycolic enzymes lead to elevated glycolytic flux and capacity, these increase the ATP and results in GSIS (glucose stimulated insulin secretion).
Mechanisms of action of GLP-1RA.
Representation of genetic variants affecting pharmacokinetics and pharmacodynamics of GLP-1 Ras. PG: plasma glucose; BMI: body mass index; HbA1C: glycemic hemoglobin, PI/I: proinsulin/insulin ratio.
Genetic variations, which affect the response to GLP-1 RAs.
Pharmacogenetics of Glucagon-like-peptide-1 receptor in diabetes management

June 2023

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1,295 Reads

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2 Citations

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Aims and scope


Pharmacia is a peer-reviewed, open access, multidisciplinary medical journal devoted to pharmaceutical and allied sciences. Topics covered are: analytics, biochemistry, biopharmaceutics, biotechnology, cell cultures, clinical pharmacy, drug delivery, drug design, drug disposition, drug stability, medicinal chemistry, metabolism, molecular modelling, basic and clinical pharmacology, pharmacognosy, pharmacodynamics and pharmacokinetics, social pharmacy, radiopharmaceuticals, toxicology.

Recent articles


Unveiling the anticancer potential of the ethanolic extract from Pometia pinnata: Molecular dynamics targeting CHK1 and cytotoxicity study on MCF-7 cells
  • Article
  • Full-text available

December 2024

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3 Reads

Henny Sri Wahyuni

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Marianne

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Sony Eka Nugraha

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[...]

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Thomi Baihaki Hijriyan

Cancer remains one of the most lethal diseases globally, with CHK1 being a critical pathway frequently altered in cancer progression. This study evaluated the anticancer and cytotoxic properties of the ethanol extract of Matoa ( Pometia pinnata ) leaves in silico and in vitro. Maceration was conducted to obtain the ethanol extract with physicochemical, pharmacokinetic, and toxicity predictions conducted using Lipinski’s Rule of Five, pkCSM, and Pro-Tox II. Molecular docking was performed using Autodock Vina and DOCK6.2, followed by molecular dynamic simulations using GROMACS. Cytotoxicity assays on MCF-7 cells were carried out using the MTT methods. The results demonstrated that the extract tested positive for flavonoids, alkaloids, tannins, saponins, glycosides, and steroids. The extract also shows potential inhibitory activity against CHK1, supported by favorable binding affinities and critical amino acid interactions. Additionally, the extract exhibited a moderate cytotoxic effect on cell MCF-7 with an IC 50 of 139 µg/mL.


Figure 3. Comparison of the PaO 2 /FiO 2 coefficient between baseline and follow-up in relation to the use of the CPAP helmet non-invasive ventilation device.
Figure 4. Comparison of the SatO 2 percentage between baseline and follow-up values obtained from patients who used the CPAP helmet non-invasive ventilation device.
Clinical and sociodemographic characteristics of the patients.
Gasometric parameters of patients with a CPAP hel- met non-invasive ventilation device.
SatO 2 percentage parameters of patients with a non-in- vasive helmet CPAP ventilation device.
Use of the high-flow helmet CPAP non-invasive ventilation device designed in Peru in patients with severe acute respiratory syndrome (COVID-19): A prospective multicenter study

José Luis Mantari

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Diego Bonifacio

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Fany Ponce Hinostroza

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[...]

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Angel T. Alvarado

High-flow non-invasive ventilation (NIV) devices reduce the morbidity and mortality of COVID-19. The objective was to evaluate the use of the non-invasive ventilation device with high-flow helmet CPAP designed in Peru in patients with severe acute respiratory syndrome (COVID-19) hospitalized in the emergency services of five hospitals. Prospective multicenter and cross-sectional observational study from five hospitals from July to August 2020. 19 patients were recruited and divided into two groups (G-1 n = 10; G-2 n = 9) applying clinical and gasometric parameters as indicators of disease evolution upon hospital admission and within 24 hours. A progressive increase in these parameters was observed in those patients who used the NIVCPAP helmet within the first 24 hours. In G-01, improvement was evident in 90% (n = 9/10): PaO 2 (range 48–137; average: 82.49 ± 8.07; p-value = 0.008), CO 2 (25.2–51.0; 36.62 ± 2.62; p-value p = 0.327), and the PaO 2 /FiO 2 coefficient (87–318; 191.5 ± 18.68). 10% of patients did not progress optimally, being subjected to endotracheal intubation and invasive mechanical ventilation. In G-02 the values were %SatO 2 (range 92–98; 96 ± 0.76) and the SaO 2 /FiO 2 coefficient (214–228; 223.2 ± 1.80), indicating significant improvement within 24 hours (p < 0.001). It is concluded that the use of the CPAP helmet non-invasive ventilation (NIV) device contributes to improving gasometric values and clinical condition. Being an alternative to recover typical cases of COVID-19 in all hospitals in Peru.


Influence of natural oils on the textural and rheological properties of cosmetic creams

December 2024

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25 Reads

Creams are semisolid dosage forms widely used for pharmaceutical and cosmetic purposes due to their pleasant appearance, easy spreadability, and the possibility to deliver hydrophobic and hydrophilic active agents. The aim of the current study was to evaluate the impact of type and concentration of different oil phases on the mechanical and rheological properties of cosmetic creams. For this purpose, a series of blank and anti-age creams were prepared applying the hot homogenization method (9000 rpm for 5 minutes). The blank creams contained an emulsifying base (Neofin Nat 8% w/w) and varying types of lipid phase: 1) babassu oil (8% w/w), 2) Cannabis sativa (2% w/w) and Camelina sativa (6% w/w) oils, 3) babassu (6% w/w) and Cannabis sativa (2% w/w) oils, and 4) babassu (6% w/w) and Camelina sativa (2% w/w) oils. The anti-age creams contained additionally Jasminum sambac flower extract (5% w/w) and Аrgireline ® solution (5% w/w). The spreading, mechanical, and rheological properties of the developed formulations were investigated. The anti-age cream based on babassu (6% w/w) and Camelina sativa (2% w/w) oils exhibited suitable textural and rheological characteristics that would facilitate its application onto skin and provide sufficient contact time to exert its beneficial effects.


Synthesis and in vitro evaluation of new oxadiazole thioethers as antibacterials

December 2024

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17 Reads

A study was conducted to synthesize a new set of compounds named comp.4–7 using the 1,3,4 tautomer of oxadiazole as the centroid unit. These compounds were subjected to various characterization processes, including thin-layer chromatography, infrared spectroscopy, and ¹ HNMR spectroscopy. The study was based on previous research that established several compounds’ diverse range of biological activities, such as hydrazide Schiff’s bases (hydrazones), oxadiazoles, thiophenes, and isoxazoles. These compounds had been found to possess properties against bacteria, fungi, TB, viruses, cancer cells, and inflammatory responses, as well as analgesic properties. The results of the docking study were conducted in MOE software, targeting the largest binding site of E. coli gyrase B (PDB: 6YD9) as identified by SITE FINDER, suggesting that these compounds had great potential to be effective antibacterial agents. To evaluate the synthesized compounds antibacterial activities, the well diffusion method was used, and the findings revealed that the synthesized compounds exhibit slight to moderate activities against E. coli , S. aureus , and K. pneumoniae .


Cardiovascular registries – bibliometric analysis of structure and characteristics

December 2024

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9 Reads

Clinical registries play an increasingly important role in determining national health policy, financial effectiveness, and generating scientific hypotheses. However, there is no universally accepted structure for these registries in Europe or worldwide. Many countries face significant challenges in organizing their clinical registries, considering the local peculiarities of the healthcare system, political organization, financial constraints, and labor capabilities. When organizing a national registry, it is essential to find the right balance between available resources, structure, and the benefits obtained—whether scientific, financial, or related to local health policy. A possible, but incomplete, quantitative assessment of the scientific usefulness of a registry can be determined through bibliometric analysis, which examines the number of unique published articles containing scientific analyses based on the respective registry. Our study aims to analyze the correlation between various registry characteristics and the scientific value of 16 national coronary registries in Europe (plus the USA), examining the number of unique published articles in PubMed.


Exploring the pharmacological mechanism of Qishen Yiqi dropping pills in treating chronic heart failure based on network pharmacology and molecular docking

December 2024

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4 Reads

Chronic heart failure (CHF) is a severe condition that affects millions of people worldwide. Despite standardized treatments, patients often face recurrent symptoms such as dyspnea, edema, and fatigue, which impair their quality of life and contribute to high mortality and hospital readmission rates. Traditional Chinese Medicine (TCM) offers alternative therapies, and Qishen Yiqi Dropping Pills (QYDP) has emerged as a potential treatment for CHF. QYDP is composed of Danshen, Huangqi, Jiangxiang, and Sanqi and is known for its ability to promote circulation, enhance Qi, and support cardiac health. Although clinical studies have suggested that QYDP can alleviate CHF symptoms, the underlying molecular mechanisms are not fully understood. In this study, network pharmacology and molecular docking were used to explore the pharmacological targets of QYDP for CHF treatment. Four core genes were identified: AKT1 , HIF1A , STAT3 , and MYC . Molecular docking confirmed the interactions between these genes and active compounds in QYDP, such as kaempferol, luteolin, quercetin, tanshinone IIa, and cryptotanshinone. These findings suggest that QYDP may treat CHF through a multitarget mechanism, offering new insights into its therapeutic potential and providing a basis for further clinical research.


Patient demographic data.
Perioperative outcomes.
Laparoscopic resections for stage IV colorectal cancer - safety and effectiveness of the method as a guarantee for an uncomplicated postoperative period and optimal pharmacotherapeutic results

December 2024

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4 Reads

Introduction : Primary tumor resection can prevent future tumor-related complications in patients with stage IV colorectal cancer. This may influence the quality of life and prevent colostomies associated with the emergency surgery. Laparoscopic approach plays an important role in attempts to reduce perioperative complications in this specific group of patients. Purpose : The aim is to assess early perioperative results in a group of 17 patients with stage IV colorectal cancer—multiple incurable liver metastases and/or pulmonary/peritoneal metastases of the disease. On the other hand, postoperative complications may delay administration of chemotherapy and influence survival. Materials and methods : We analyze retrospectively the perioperative results in a group of 17 patients with laparoscopic palliative colorectal resections for stage IV colorectal cancer. Assessment includes perioperative complications, median hospital stay, perioperative blood loss, need for blood transfusion, operative time, and type of surgical procedure. Results : We performed totally laparoscopic 10 sigmoid resections, five left colectomies, and two right colectomies. Fourteen simultaneous liver biopsies were performed during laparoscopy. No perioperative deaths were registered. Perioperative mortality rate is 0%. Perioperative morbidity rate is 0%. No perioperative complications. The median perioperative stay is 5.3 days. Median blood loss is 47.9 mL. Overall, three units of blood were transfused. The median transfusion rate is 0.17 units per patient. The median operative time is 130.2 minutes. Conclusion : The laparoscopic approach is associated with very good perioperative results in patients with stage IV colorectal cancer and palliative resection of the primary tumor. Early hospital discharge and minimal operative trauma may not influence early administration of chemotherapy.


Pentoxifylline ameliorates carbamazepine-induced hepatotoxicity via down expression of CYP3A4 and NF-kB gene expression in the rat: in vivo study

December 2024

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10 Reads

Drug-induced liver injury (DILI) is a serious complication of many drugs, including carbamazepine; this study investigates the protective effect of pentoxifylline (PTX) against DILI induced by carbamazepine in rat models by attenuating CYP3A4 and NF-κB gene expression. Forty rats were divided into five groups: the control group received no treatment, the induction group received 50 mg/kg carbamazepine orally for 28 days, and three groups received PTX (100, 200, and 300 mg/kg) once daily for one hour before carbamazepine induction for 28 days. Then, the rats were euthanized, and blood and liver tissue were collected for biochemical, gene expression, and histopathology. PTX attenuates the carbamazepine-induced increased CYP3A4 and NF-κB gene expression, with the highest dose showing the best result. PTX also reduced aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, while glutathione levels increased. In conclusion, PTX is highly efficacious in preventing and restoring the liver cells’ normal morphology and cellular function caused by carbamazepine hepatotoxicity. A possible mechanism of the PTC effect is hindering oxidative stress by scavenging free radicals and enhancing the body’s natural defense antioxidant system. Additionally, it exerts an anti-inflammatory impact by modulating NF-κB gene expression.


Health-related quality of life after Rituximab treatment of patients with antineutrophil cytoplasmic antibody-associated vasculitis

November 2024

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11 Reads

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are severe, socially significant diseases that require a clear understanding of the relationship between the current health status and quality of life of patients. On the one hand, in the scientific literature, there is not enough data to assess the quality of life for the different therapeutic regimens, and no specific tools have been developed to assess functional indicators and health status. On the other hand, with the exception of Rituximab treatment, the available immunosuppressive regimens do not lead to a good clinical response in patients with AAV. The aim of the study is to measure health-related quality of life in a Bulgarian population of patients with systemic vasculitis associated with ANCA undergoing biological treatment with Rituximab by using the generic instrument SF-36 version 2. We conducted a retrospective-prospective, non-interventional, controlled study in two periods in two centers in Bulgaria. Treatment with Rituximab leads to qualitative and quantitative improvement in all components of physical health, including mental and social components. After treatment, all measured parameters were within the normal range for the general population.


Some selected models of imidazo[1,2-a]pyridine derivatives possessing different biological activity.
Schematic representation of the reaction process for the synthesis of O-methylvalerolactim 4.
Schematic representation of the reaction process for the synthesis of 3-hydroxy-1-(4¹-methoxyphenyl)-3-aryl-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromides 10 a-k and 11 a-f, i, l.
Schematic representation of the reaction process for the synthesis 1,3-bis-(4¹-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-1-ium bromide 12 c.
Syntheses and evaluation of novel 3-hydroxy-1,3-diaryl-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromides as potential anticancer agents

November 2024

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1 Read

New 3-hydroxy-1,3-diaryl-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromides have been designed, synthesized, and characterized by ¹Н NMR, ¹³C NMR, and LCMS. The cyclic structure of the condensation products of aryl-(3,4,5,6-tetahydropyridin-2-yl)amines with α-bromoketones has been proven. It has been shown that heating 3-hydroxy-1,3-bis-(4¹-methoxyphenyl)-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromide in acetic anhydride accompanied by elimination of water to form 1,3-bis-(4¹-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-1-ium bromide. Antitumor activity of 1,3-bis-(4¹-ethoxyphenyl)-3-hydroxy-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromide and 1,3-bis-(4¹-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-1-ium bromide have been studied. The fully aromatic imidazo[1,2-a]pyridine-1-ium bromide system was shown to have a higher antitumor effect. According to the screening results, the tested compound showed a significant level of anticancer effect on cancer cells of colon COLO 205 (lgGI50 = -5.35, lgTGI = –4.70 and lgLC50 = –4.19) and melanoma SK-MEL-5 (lgGI50 = –5.57, lgTGI = –4.81 and lgLC50 = –4.17).


Unveiling the dual anti-viral and anti-bacterial potential of Tridax procumbens: integrating system biology and molecular modeling for therapeutic insights

November 2024

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23 Reads

This study evaluates the dual anti-viral and anti-bacterial activity of Tridax procumbens using system biology and molecular docking targeting the tumor necrosis factor (TNF) signaling pathway. The bioactive potential of Tridax procumbens was studied using phytochemical databases, and the essential biomolecules were selected for the study. The principle of geneVenn diagrams and protein target prediction was used to identify overlapping molecular targets with viral and bacterial diseases, which was later validated using various database mining tools like GeneCards and OMIM. Cytoscape software was applied to construct protein-protein interaction networks, which showed that TNF, AKT1, EGFR, SRC, and ESR1 are the hub genes of the networks. The gene ontology (GO) enrichment analysis also recapitulated the modulated biological processes, cellular components, and molecular functions of Tridax procumbens compounds, including their action on the TNF signaling in inflammation and immune responses. Molecular docking studies showed strong binding affinities of compounds such as cynaroside and 5,7,2,3,4-Pentahydroxy-3,6-dimethoxyflavone 7-glucoside to TNF, and molecular dynamics simulations confirmed these interactions’ stability. The findings suggest that Tridax procumbens exerts its therapeutic effects by modulating the TNF signaling pathway, offering significant anti-viral and anti-bacterial properties. This integrative approach provides insights into the Tridax procumbens’s mechanisms of action, supporting its potential as a source of novel therapeutic agents against infectious and bacterial diseases. There is still a need for further experimental research to define the full spectrum of Tridax procumbens’ therapeutic application.


Anti-inflammatory potential of Curcuma heyneana: An in vitro and in silico investigation

November 2024

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60 Reads

Rheumatoid arthritis (RA) is a progressive and chronic systemic autoimmune disease. However, currently treatment is often carried out using NSAIDs and corticosteroids. Although it reduces symptoms, this treatment has a high rate of side effects. This study aims to determine the anti-inflammatory property of Curcuma heyneana so that it can be used as an alternative treatment for RA. Based on author knowledge, this study on C. heyneana from the Indonesian region for the treatment of RA is still limited. C. heyneana’s rhizome was extracted by maceration with ethanol followed by fractionation process using n-hexane, ethyl acetate, and n-butanol. The anti-inflammatory invitro activities were determined by heat-induced hemolysis, effect on protein denaturation, and cyclooxygenases (COX) inhibition assay. Molecular docking of major predictive compounds was performed by AutoDock Vina. The results showed that some fractions of C. heyneana contained terpenoids, flavonoids, and alkaloids. The ethyl acetate fraction exhibited the highest anti-inflammatory activity, which was attributed to the presence of curcuminoids. Molecular docking studies further confirmed the potential of demethoxycurcumin, a curcuminoid identified in the ethyl acetate fraction, to inhibit COX-2. These findings suggest that C. heyneana, particularly its previously unreported curcuminoid-rich fractions, holds promise as a natural anti-inflammatory agent. Further research is warranted to explore the therapeutic potential of this plant in the management of RA and other inflammatory disorders.


Challenges and opportunities of Italian-qualified pharmacists relocated to work in Great Britain: A cross-sectional survey

November 2024

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10 Reads

Background: The Italian university system is actively revising the Master of Pharmacy (MPharm) curriculum to reflect post-COVID healthcare needs and a greater clinical focus. Understanding the challenges and opportunities faced by Italian pharmacists that relocated to Great Britain (GB) might provide valuable insights regarding the transferability of knowledge and skills obtained in the Italian pharmacy degree. Aim: The study aimed to capture the perceptions of Italian pharmacists practising in GB regarding the Italian pharmacy degree programme and to explore the challenges and opportunities they face in their new professional environment, ultimately to inform the Italian government and related stakeholders (Ministry of University and Research, MUR) about the need to update the Italian MPharm curriculum to make it more clinically relevant and aligned with international standards. Materials and methods: The authors developed a 50-item survey, pilot tested and reviewed for face and content validity by an expert panel. Participants’ characteristics, reasons for moving to GB, and data on their experience of practising as a pharmacist in Italy and GB were collected using Likert-type items and open- and closed-ended questions. Convenience sampling was used, and a sample power calculation was not deemed necessary. Statistical analysis involved descriptive analysis presenting frequencies and percentages for Likert-type and categorical items. Results: An estimated 281 pharmacists qualified in Italy are registered with the General Pharmaceutical Council in GB. Of these, 54 took part in the survey, resulting in a probable coverage of the sample population of 19.2%. Respondents pointed to the lack of job satisfaction and limited future perspectives as the main reasons to leave Italy (38.9% and 83.3%, respectively). Other reasons to relocate to GB were clinically focused job opportunities and better salaries (68.5% and 79.6%, respectively). Notably, almost two-thirds of the participants affirmed that Italian pharmacy degrees were insufficient to meet the requirements for practising as a pharmacist in GB. Conclusion: Different approaches to teaching clinical pharmacy and practical aspects seen in the pharmacy degree programmes in Italy and GB highlight a clear need for aligning the Italian pharmacy curriculum with the modern requirements of the pharmacy profession. Additionally, this alignment would facilitate the movement of Italian pharmacists into the GB healthcare system and beyond.


Preparation and characterization of amphiphilic cream formulations with meloxicam

November 2024

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11 Reads

The purpose of this study is to formulate and evaluate amphiphilic cream with meloxicam indicated for topical relief of pain, particularly because there are currently no available topical dosage forms on the market. Thus, the present research is focused on characterization of the capacity of the amphiphilic base, composed of glycerol monostearate, cetyl alcohol, Tagat® S2, Myritol® 318, propylene glycol, and white petrolatum, to be loaded with drug model meloxicam dissolved in propylene glycol. To enhance the solubility and penetration of meloxicam, menthol as a rubefacient was added to the meloxicam solution. The series of three formulations were prepared with variable content of added menthol. Obtained creams were characterized by drug content, pH, spreadability, viscosity, microbial purity, drug release, and stability. Results showed stable cream formulations with good spreadability and viscosity, suitable for topical application.


Fluorescence microscopy images of human colorectal adenocarcinoma cells (HT-29). Upper panel: Acridine Orange (AO)/Ethidium Bromide (EtBr) double staining; Lower panel: DAPI staining. (a, d) Untreated HT-29 cells; (b, e) HT-29 cells treated with 18.5 µM BA; (c, f) HT-29 cells treated with 3.8 µM [ProOEt][BA].
The effect of 5 µM and 10 µM BA or [ProOEt][BA] on the IL1B gene expression of PBMC after stimulation for 6 h. The results are presented as the mean ± SE and 1.96*SE of a fold of change in the IL1B compared to the calibrator (non-treated cells–N) after normalization to the reference genes B2M and GAPDH. *p < 0.05.
Anti-colon cancer activity of amino acid ester betulinates: Apoptosis induction and IL1B gene expression in PBMCs by the lead compound

November 2024

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22 Reads

Betulinic acid (BA) is a natural pentacyclic triterpenoid with significant pharmaceutical potential. We found that converting BA into amino acid ethyl ester salts alters its cytotoxic effect on colorectal adenocarcinoma cells (HT-29). Among these salts, the estimated half-maximal inhibitory concentration (IC50) at 72 h varies by up to fifteenfold. The proline ethyl ester [ProOEt] salt, the most active compound, exhibited an IC50 value of 3.8 µM, which is 4.8 times lower than that of the parent BA. We observed that exposure to BA or [ProOEt][BA] induced apoptosis in HT-29 cells. Additionally, the proline-based salt led to a higher level of IL1B gene expression in PBMCs at a lower stimulation concentration.


Pharmacovigilance study of tyrosine kinase inhibitors: Analysis of adverse reactions

November 2024

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13 Reads

The aim of the study is to analyze reports of adverse drug reactions published in the scientific literature occurring during and after the use of kinase inhibitors for the treatment of rheumatologic diseases to determine their type, frequency, and severity. The search was conducted in the MEDLINE and PubMed databases from January 2005 to May 2022. We found a total of 291 publications, from which we selected suitable ones for data extraction. We conducted descriptive and variation analyses as the main statistical analyses. We determined mean values, standard deviation, minimum, maximum, and 95% confidence intervals. The PICOS tool was used to evaluate the results. The analyzed population includes patients with rheumatologic and oncologic diseases. There is a significant interest in the drug safety of kinase inhibitors, as they represent a rapidly evolving and reliable pharmacological class. Clarifying the safety profile of their representatives remains important. In-depth review of full-text publications shows that the high frequency of reported serious ADRs is rather due to increased interest in reporting and publishing these cases than to their high frequency of occurrence.


Frequency of the spontaneous chromosomal fragility in patients with polygene multifactor disorders and in healthy controls.
Samples showing some general biochemical and morphological characteristics between rodent brain, pancreas, and myocardium: A, B, D, E, G, H are average titers in total organ lysates and in samples containing selected molecules possessing affinity to GSH by passing through an agarose-GSH column. A of the anti-ganglisodie antibodies in samples of rodent brain; B of the gangliosides in samples of rodent brain; D of the anti-ganglisodie antibodies in samples of rodent pancreas; E of the gangliosides in samples of rodent pancreas; G of the anti-ganglioside antibodies in samples of rodent myocardium; H of the ganglisodies in samples of rodent myocardium. On the abscise are shown the dilutions of the respective biological samples in µM/g tissue material, and on the ordinate are the values of the optical density (OD); C, F, I, L are fixed histological preparations, stained by H/E; C of rat brain; F of rat pancreas; I of rat myocardium; and L of rat liver.
Agarose gel electrophoresis of samples from mature cells of adult experimental mice: A: presence (lanes 2 and 4) and expression (lanes 3 and 5) of tumor suppressor gene HACE-1 in each one of the two inbred lines of experimental mice: lanes 2 and 3 – in WTDcn1+/Dcn1+ homozygotes; lanes 4 and 5 – in partially KDDcn1+/Dcn1- heterozygotes, assessed by standard PCR (lanes 2 and 4) and RT-PCR (lanes 3 and 5). Specific primers, complementary to the cellular DNA genome, were applied. Lane 1: specific molecular marker (M) with size 750–2500 bp. B: in Balb/c experimental mice: lanes 2–6: normal presence (lane 2–4) and expression (lanes 5 and 6) of oncogene Dcn-1; normal presence (lanes 8–10) and expression (lanes 11 and 12) of the opposite tumor suppressor gene HACE1 in mature epithelial cells from the skin of an adult animal, assessed by standard PCR (lanes 2–4 and 8–10) and RT-PCR (lanes 5, 6, 11, and 12). Specific primers, complementary to the cellular DNA genome, are applied. Lane 1: specific molecular marker (M) with size 750–2500 bp.
Experimental in vivo models for understanding inter-molecular interactions and preventing multifactor disease development

November 2024

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5 Reads

The increased spontaneous fragility in the centromere regions of the chromosomes predisposes to abnormal cellular division due to abnormal interaction with the mitotic spindle, which leads to number chromosomal aberrations. The abnormal structure of the microtubule-associated proteins (MAPs) could also be among the internal factors, predisposing to these pathologies. On the other hand, the increased frequency of the spontaneous chromosomal fragility suggests abnormal structure of the respective chromosomal/chromatin components and thus an increased risk about gene mutations and structural chromosomal aberrations. The spontaneous chromosomal fragility was tested by light microscopy observation of metaphases from peripheral blood lymphocytes of 8 patients with polygene pathologies (neoplasms, neuro-degenerative diseases, and neuro-psychiatric disorders) and of 18 healthy controls. In the tested patients was established significantly higher frequency of the spontaneous chromosomal fragility, including in the centromere chromosomal regions, compared to the controls. Different inter-molecular interactions, which could prevent the pathology appearance, were investigated by appropriate experimental in vivo models. As a whole, in the most cases, the presented data showed significantly lower average titers of anti-ganglioside antibodies and gangliosides in the samples from myocardium and liver than in the samples from brain and pancreas. By taking into consideration that the myocardium and liver are known as the most enriched of GSH anatomic organs, the presented data could be explained with the literature messages of higher amounts of de novo-synthesized free GSH tri-peptide in the same two organs. Moreover, a possibility about the production of antibodies/immunoglobulins by non-lymphoid types of cells, tissues, and organs in appropriate conditions was shown. Because the so-produced antibodies are out of the germinative centers in the specialized lymphoid tissues and organs, the control of their functions by small ions and molecules as gangliosides is very important. In the current study, the attention was particularly directed to the iteractions with the participation of gangliosides, the reduced form of the tri-peptide glutathione (GSH), and the protein HACE1. Besides the tumor-suppressor activity of protein HACE1, also its neuroprotective influence was proven, namely by interactions with specific molecules.


Inhibition of selective factor Xa suppresses type 1 diabetes development in mice via the CXCL16 chemokine

November 2024

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30 Reads

Type 1 diabetes mellitus (T1DM) is associated with enhanced thrombosis potential. This research aims to investigate the role of coagulation system activation and CXCL16 in T1DM progression and the possible preventive effect of the selective Factor Xa inhibitor, Fondaparinux (Fond). Forty male Wistar albino mice were classified into 4 groups. Control, Fond, Streptozotocin (STZ), and Fond + STZ groups. Biochemical, hematological, and histopathological parameters, expressions of CXCL16, insulin, fibrinogen, and PAR-2, were investigated. A significant increase in blood glucose level and expressions of CXCL16, fibrinogen, and PAR-2, together with histological and nuclear changes in the pancreatic islets, was observed in STZ-treated mice, accompanied by a reduction in the serum insulin level. Fond improved the deleterious effects resulting from STZ treatment. In conclusion, coagulation system activation and CXCL16 play a critical role in the initiation of T1DM and could be used as therapeutic targets for T1DM prevention.


Molecular simulation-based evaluation of anti-inflammatory properties of natural compounds derived from tobacco (Nicotiana tabacum L.): Computational multi-target approaches

November 2024

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25 Reads

Various components of the tobacco plant (Nicotiana tabacum L.) have undergone pharmacological assessment to highlight their traditional role in addressing different health conditions. The anti-inflammatory properties of thirteen natural substances were investigated through the use of molecular docking conducted with AutoDock 4.2.6 Tools and Molecular Dynamics Simulations (MDS) executed with GROMACS 2016.3. ADME characteristics were assessed using SwissADME (absorption, distribution, metabolism, and excretion). Chlorogenic acid and rutin, plant-derived natural compounds, showed substantial binding tendencies with cyclooxygenase-1 (COX-1), phosphodiesterase-4 (PDE4), cyclooxygenase-2 (COX-2), phosphodiesterase-7 (PDE7), interleukin-17A (IL-17A), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and prostaglandin F synthase. Rutin emerged as the most notable among the tested compounds (docking energy: −11.0 kcal/mol against PDE7 and prostaglandin F synthase). Chlorogenic acid also displayed substantial and noteworthy binding energies of −9.4 kcal/mol with PDE4 and PDE7 receptors. Consequently, these investigated natural compounds could potentially serve as agents that reduce inflammation and require additional in vitro and in vivo studies to aid the creation of new anti-inflammatory drugs.


Titers of GM3 ganglioside and anti-GM3 antibodies in extracts from rodent brain (A, B), rodent pancreas (C, D), rodent myocardium (E, F), rodent liver (G, H), rodent small intestine (I, J); A, C, E, G, I—control samples; B, D, F, H, J—containing molecules possessing affinity to tripeptide GSH.
Titers of ganglioside GM1 and anti-GM1 antibodies in extracts from rodent brain (A, B), rodent pancreas (C, D), rodent myocardium (E, F), rodent liver (G, H), rodent small intestine (I, J); A, C, E, G, I—control samples; B, D, F, H, J—containing molecules possessing affinity to tripeptide GSH.
Titers of GD1a ganglioside and anti-GD1a antibodies in extracts from rodent brain (A, B), rodent pancreas (C, D), rodent myocardium (E, F), rodent liver (G, H), rodent small intestine (I, J); A, C, E, G, I—control samples; B, D, F, H, J—containing molecules possessing affinity to tripeptide GSH.
Production of anti-GM3, anti-GM1, and anti-GD1A antibodies by non-lymphoid cells, tissues, and organs

November 2024

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4 Reads

Gangliosides are acidic glycosphingolipids localized mainly on the outer membrane layer of the membranous cell structures. These molecules participate in important mechanisms at molecular, cellular, tissue, organ, and organism levels. It has been proven that gangliosides play a role as regulators of various biological processes but also as markers in a number of multifactor pathologies. In this regard, the present study determined the titers of the GM3, GM1, and GD1a gangliosides, as well as the titers of IgG-class antibodies against each of them by enzyme-linked immunosorbent assay (ELISA), in several different anatomic organs: brain, pancreas, myocardium, liver, and small intestine from rodents. A total extract (control sample) containing the complete set of molecules is prepared from each isolated anatomic organ. An equivalent amount of the extract is passed through a GSH-agarose column in order to select the molecules from each organ possessing affinity to the reduced form of glutathione tripeptide (GSH). GSH is known as an antioxidant, immunomodulator, cardioprotector, neuroprotector, hepatoprotector, anticancer, and antiaging agent. As a whole, significantly lower titers of the three gangliosides and the antibodies to them are reported in the myocardium and liver samples compared to the brain and pancreas samples. Taking into account that the myocardium and liver are the organs known with the highest content of GSH, the obtained results can be explained by the possibly high content of free and/or newly synthesized GSH in them, which does not participate in intermolecular interactions compared to the other investigated organs. Complete absence of each of the three tested gangliosides or of antibodies against them at certain dilutions of the small intestine samples, as well as the highest titers of the same parameters compared to the corresponding samples from the other organs of each of the gangliosides or of the specific antibodies at other dilutions, is observed. One of the explanations for those peculiarities is associated with the presence of the intestinal microflora, including the influence of intestinal bacteria neuraminidases (sialidases). The presented data also show a possibility of antibodies/immunoglobulins production by non-lymphoid cells, tissues, and organs in suitable conditions. Since the immunoglobulins thus produced reside outside the germinal centers of the specialized lymphoid tissues and organs, regulation of their production and functions by interactions with small ions and/or molecules is also important. Gangliosides are namely such small molecules. Special attention is paid to intermolecular interactions involving the listed gangliosides and GSH. The main objective is related to understanding the mechanisms underlying the interaction between the individual organs and systems in the body.


Metabolic differences between normal and cancer cells.
How IGF-1 plasma levels affect the proliferation and apoptosis of normal and cancer cells.
Oncology-related dietary approaches.
From weight loss to cancer treatment: Fasting as an adjuvant anticancer therapy

October 2024

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47 Reads

The number of studies that have been conducted on the possible benefits of different types of fasting or calorie restriction on cancer therapy, including the likelihood that these treatments lessen side effects, has been limited. However, the results are nevertheless promising. Chemotherapy’s adverse effects have led to a quest for options that reduce reliance on it. The susceptibility of tumorous cells to specific metabolites and nutrient deficiency is increasingly recognized as a key characteristic of the disease. This review delves into the data on various fasting methods and calorie restriction in rodents and humans, with a focus on biological adaptations that could potentially lower cancer risk or enhance cancer treatment results. We also emphasize recent scientific developments regarding the use of prolonged fasting and fasting-mimicking diets as a possible additional treatment for patients receiving immunotherapy or other treatments. This approach shows promise in enhancing treatment effectiveness, preventing resistance, and minimizing side effects. This study proposes that combining fasting and calorie restriction with chemotherapy, immunotherapy, or other therapies might be a potential technique to improve treatment efficacy, avoid resistance, and reduce adverse effects.


Trends and motives in the post-graduate professional orientation of the young doctors of the 2023 class of Medical University-Sofia

October 2024

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10 Reads

The grown-up individual’s need for self-affirmation is a unified whole with his professional and labor activity and with the successful realization in it. For this reason, professional choice is a complex decision-making process, determined by social and personal factors, as it is dictated not only by the needs of society, but also by the interests, opportunities, needs and inclinations of the individual. In view of this, the present article will present and analyze data from an empirical study investigating the trends, motives and conditions in the professional orientation of young doctors of the 2023 Class of Medical university-Sofia.


Frequency of top 10 potential drug-drug interactions among hospitalised haemodialysis patients.
The top 10 class C/D drug-drug interactions among hospitalised haemodialysis patients.
shows the association between drug-drug interactions and in-hospital mortality among haemodialysis patients.
Factors associated with potential drug-drug interactions among hospitalised haemodialysis patients.
Assessing drug-drug interactions: Prevalence, predictors, and their impact on in-hospital mortality in hospitalised haemodialysis patients

October 2024

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17 Reads

This retrospective observational study was conducted in Libya to examine the frequency and determinants of drug-drug interactions (DDIs) among hospitalised haemodialysis inpatients between January 2018 and June 2020. The study highlighted a notable prevalence of DDIs among HD patients, with a prevalence rate of 71.1%. Regarding the identification of DDI predictors and their correlations with extended hospital stays and polypharmacy, regression analysis was conducted to identify predictors and outcomes. The study found that DDIs were associated with prolonged hospital stays and were independently linked to polypharmacy in HD patients. Furthermore, a significant clinical impact of DDIs on HD patients was observed, particularly in relation to in-hospital mortality.


Location of water samples.
Separation of seven low-mg/L inorganic anion standard solutions: 1-F- 1 mg/L, 2-Cl- 1.5 mg/L, 3-NO2- 1.5 mg/L, 4-Br- 5 mg/L, 5-NO3- 1 mg/L, 6-PO4³⁻2.5 mg/L, 7-SO4²⁻ 7.5 mg/L.
Calibration curves of analyzed anions.
Chromatogram of inorganic anions in drinking water from Yerevan, Kentron district.
Method specificity test results for identifying fluoride, chloride, nitrite, bromide, nitrate, phosphate, and sulfate ions (n = 6).
Ion-chromatographic determination of common anions in drinking water in some regions of the Republic of Armenia

October 2024

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21 Reads

The present study investigated the anion composition of drinking water from various cities and villages in Armenia, including spring water and tap water samples. The simultaneous separation was achieved for fluoride, chloride, bromide, nitrite, nitrate, sulfate, and phosphate anions with the correlation coefficients >0.998. Validation of the method was carried out in accordance with the requirements of guidelines in terms of selectivity, specificity, system suitability, linearity, accuracy, precision, lower limits of detection and quantitation, robustness, and stability. The method was suitable for routine drinking water quality assessment in line with the national or World Health Organization (WHO) regulations. The validated method was further used to analyze drinking water samples from different regions of Armenia. The observed concentrations for the anions in drinking water complied with the WHO limits for drinking water with some exceptions. The test method can be submitted to quality control laboratories as a convenient and practical tool for routine analysis and monitoring studies.


Assessment of inflammatory markers in cardiac tissue A. TNF-alpha; B.IL-6. One-way ANOVA with post hoc Tukey test, *** indicate p-value ≤ 0.001, and **** indicate p-value ≤ 0.0001.
Assessment of oxidative stress markers in cardiac tissue. A.MDA levels; B.SOD levels. One-way ANOVA with post hoc Tukey test, * indicates p-value ≤ 0.05, ** indicate p-value ≤ 0.01, and **** indicate p-value ≤ 0.0001.
Assessment of skin markers. A. Collagen 1; B. Elastin. One-way ANOVA with post hoc Tukey test, *** indicate p-value ≤ 0.001, and **** indicate p-value ≤ 0.0001.
Light microscope histopathological images of hematoxylin- and eosin-stained cardiac tissue. A. G1: no treatment; B. G2: induction group; C. G5: 1 mg/kg canagliflozin, and D. G4: 3 mg/kg canagliflozin. The black arrow indicates normal cardiac cells and normal nuclei, and the blue arrow indicates bizarre, irregular, and hyperchromatic nuclei. X40.
Canagliflozin exerts anti-inflammatory and antioxidant effects in the heart and skin tissues: Biochemical and histopathological assessment in a model of accelerated aging induced by D-galactose in mice

October 2024

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22 Reads

Canagliflozin was assessed for its anti-inflammatory and antioxidant effects as an anti-aging drug in animal models. 50 Swiss albino male mice were divided into five groups; all groups received their intervention using gastric gavage; group 1 received normal saline for 14 weeks; group 2 received induction by D-galactose 200 mg/kg/day for seven weeks; and group 3 to 5 received the same induction for seven weeks, followed by another seven weeks of investigated drugs; group 3 received Vitamin C (100 mg/kg/day); group 4 received canagliflozin (3 mg/kg/day); and group 5 received canagliflozin (1 mg/kg/day). At the end of 14 weeks, all animals were euthanasiad, and heart and skin tissue were harvested for further analysis. Canagliflozin at both 1 and 3 mg/kg was successful in reducing the levels of inflammatory mediators (TNF-alpha and IL6), reducing levels of MDA, increasing the levels of SOD, and increasing the levels of collagen-1 and elastin in skin tissue. Additionally, 3 mg/kg Canagliflozin showed a better effect compared to 1 mg/kg regarding its effect on IL6, SOD, and elastin. Histopathologically, treatment with both doses of Canagliflozin attenuates abnormalities induced by D-galactose (bizarre, irregular, and hyperchromatic nuclei). Canagliflozin exhibits potent antioxidant and anti-inflammatory effects in living organisms, effectively prevents cardiac and skin damage generated by D-galactose, and possibly reduces aging.


Journal metrics


1.1 (2022)

Journal Impact Factor™


41%

Acceptance rate


2.4 (2022)

CiteScore™


24 days

Submission to first decision


31 days

Submission to final decision


0.212 (2022)

SJR


EUR 800

Article processing charge

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