Frontiers in Pharmacology

Background Multidrug resistance (MDR), mainly caused by ATP-binding cassette transporters (ABCTs) efflux, makes it difficult for many anticancer drugs to treat breast cancer (BC). Phytochemicals can reverse cancer’s MDR by modifying ABC transporter expression and function, as well as working synergistically with anticancer drugs to target other molecules. The reversal effect of the isoquinoline alkaloid coptisine (COP) was assessed on four breast cell lines; Two sensitive MCF-7 cell lines with positive estrogen, androgen, progesterone, and glucocorticoid receptors, as well as MDB-MB-231 cells with negative estrogen, progesterone, and HER2 receptors, and two doxorubicin-resistant cell lines, MCF-7/ADR and MDB-MB-231/ADR. Methods The cytotoxicity of COP and its ability to improve doxorubicin (DOX) cytotoxicity were assessed using the MTT assay. The effectiveness of COP in reversing DOX resistance was evaluated by calculating resistance ratio (RR) values, combination index (CI), and isobologram (IB). The inhibitory effect of COP on ABCT efflux function in comparison to verapamil (VER) was evaluated by measuring the cellular accumulation of Rho123 using flow cytometry. The impact of COP, either alone or in combination with DOX, on the gene expression of ABCTs (P-gp/MDR1, BCRP, and MRP1) of investigated cell lines was assessed by RT-PCR. Results The COP showed modest cytotoxicity on the examined cell lines. In MCF-7/ADR and MDA-MB-231/ADR cells, COP (31 μM) enhanced DOX cytotoxicity with CI (0.77 and 0.75), RR (2.58 and 3.33), and IB suggesting synergism. COP significantly inhibits ABCT function in resistant BC cell lines, increases Rho123 accumulation, and decreases efflux more than VER; 2.1 and 1.2-fold, respectively. The combination of COP and DOX had a strong inhibitory effect on ABCT function (3.1 and 3.9 times VER, P< 0.001) and downregulated the genes and protein expression of ABCT. Conclusion COP reversed ABCT-mediated multidrug resistance in vitro , indicating its potential as a multidrug resistance-reversing agent in cancer chemotherapy.

Vulvodynia is a chronic pain condition that affects the vulvar area, often resulting in significant discomfort and a reduced quality of life. Current treatments for vulvodynia are limited, and there is a need for more effective therapeutic options. Acmella oleracea, known for its spilanthol content, and Boswellia serrata, rich in boswellic acids, have been explored for their potential analgesic properties in pain management. In this study, vulvodynia-like symptoms were induced in female mice using Complete Freund’s adjuvant (CFA). After the induction of symptoms, the mice were treated with a combination of Acmella oleracea and Boswellia serrata extracts (AO + BS). Behavioral pain assessments were conducted to monitor the effects of the treatment. Additionally, biochemical and functional evaluations were performed to measure spinal microgliosis and neuronal overexcitation. The combination of Acmella oleracea and Boswellia serrata (AO + BS) resulted in a significant reduction of vulvar hypersensitivity in mice. Besides alleviating pain, AO + BS therapy also reduced spinal microgliosis and neuronal overexcitation in mice with vulvodynia. The findings suggest that the AO + BS combination has the potential to alleviate vulvodynia associated pain through mechanisms involving the reduction of spinal microgliosis and neuronal overexcitation. These results point to the therapeutic promise of these plant extracts for chronic pain conditions like vulvodynia. The combination of Acmella oleracea and Boswellia serrata shows potential as a treatment for vulvodynia. However, further studies are needed to explore the underlying mechanisms and to optimize the dosage for clinical use.

Neurodegenerative diseases (NDDs) represent a category of serious illnesses characterized by the progressive deterioration of neuronal structure and function. The exploration of natural compounds as potential therapeutic agents has gained increasing attention in recent years owing to their wide range of pharmacological activities and minimal side effects. Baicalin (BAI) and baicalein (BE), polyphenolic flavonoids, derived from the root of Scutellaria baicalensis , evidently show potential in treating NDDs. This review provides an overview of the current understanding of the roles of BAI and BE in alleviating neuroinflammation, a pivotal pathological process implicated in various NDDs. Studies conducted prior to clinical trials have shown that BAI and BE exert protective effects on the nervous system in different animal models of NDDs. Furthermore, mechanistic studies indicate that BAI and BE exert anti-inflammatory effects by inhibiting pro-inflammatory cytokines, suppressing microglial activation, and regulating microglial phenotypes. These effects are mediated through the modulation of inflammatory signaling cascades, including Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), amp-activated protein kinase (AMPK), NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, and nuclear factor erythroid 2-related factor 2 (Nrf2)/hemoglobin oxygenase-1 (HO-1). Overall, BAI and BE exhibit promising potential as natural compounds with anti-inflammatory properties and offer innovative therapeutic approaches for managing NDDs.

Renal fibrosis (RF) is a pathological process characterized by the excessive accumulation of extracellular matrix (ECM), which triggers a repair cascade in response to stimuli and pathogenic factors, leading to the activation of molecular signaling pathways involved in fibrosis. This article discusses the key cells, molecules, and signaling pathways implicated in the pathogenesis of RF, with a particular focus on tubular epithelial cells (TECs), cellular senescence, ferroptosis, autophagy, epithelial-mesenchymal transition (EMT), and transforming growth factor-β(TGF-β)/Smad signaling. These factors drive the core and regulatory pathways that significantly influence RF. A comprehensive understanding of their roles is essential. Through a literature review, we explore recent advancements in traditional Chinese medicine (TCM) aimed at reducing RF and inhibiting chronic kidney disease (CKD). We summarize, analyze, and elaborate on the important role of Chinese herbs in RF, aiming to provide new directions for their application in prevention and treatment, as well as scientific guidance for clinical practices.

Resistance to chemotherapeutic agents poses a significant challenge in cancer treatment, particularly with doxorubicin, a widely used drug for various cancers, including breast cancer, leukaemia, osteosarcoma, and gastrointestinal cancers. This review aims to elucidate the critical role of microRNAs (miRNAs) in the development of doxorubicin resistance, focusing on their interactions with ATP-binding cassette (ABC) transporters. Despite extensive research, the molecular mechanisms governing doxorubicin resistance still need to be completed, particularly regarding the regulatory influence of miRNAs on ABC transporter expression. By analyzing current literature, this review identifies a notable gap: the lack of comprehensive insight into how specific miRNAs modulate the expression and activity of ABC transporters in cancer cells, contributing to doxorubicin resistance. We systematically examine recent findings on the interplay between miRNAs and ABC transporters, providing a detailed assessment of potential therapeutic strategies that leverage miRNA modulation to overcome drug resistance. Ultimately, this review underscores the significance of integrating miRNA research into existing therapeutic frameworks to enhance the efficacy of doxorubicin in cancer treatment.

Targeted therapy has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients carrying common EGFR mutations, but the standard care for patients with rare mutations has not been well established. Here, we report a 65-year-old female diagnosed with stage IIIC lung adenocarcinoma located in the right inferior lobe, harboring uncommon EGFR L858M/L861R mutations. Remarkably, 24 days post-treatment of afatinib and anlotinib, chest CT scans demonstrated significant shrinkage of primary lesion, indicating a partial response. Except for mild hand-foot syndrome and diarrhea, no other severe adverse symptoms were observed throughout treatment. The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations.

Ziziphi Spinosae Semen (ZSS) is the seeds of Ziziphus jujuba Mill. var. Spinosa (Bunge) Hu ex H. F. Chou, which has the effects of nourishing heart and liver, tranquilizing heart and tranquilizing mind. With the development of research on the metabolites of ZSS, more than 160 metabolites have been isolated from ZSS, including saponins, alkaloids, flavonoids, fatty acids, volatile oils, polysaccharides and proteins. The active metabolites of ZSS have regulatory effects on the nervous system, cardiovascular system, hematopoietic system, immune system and substance metabolism, and have various pharmacological effects such as anti-oxidation, anti-aging and anti-cancer. Although many traditional uses of ZSS have been clarified, the relationship between its structure and function remains to be further studied. This article provides a review of the metabolites, pharmacological activity, pharmacokinetics and toxicology of ZSS, and explores the future research prospects and existing problems of ZSS, so as to provide reference for further research and establishment of quality control standards of ZSS.

Background In the treatment of depression, medication plays a crucial role. However, insufficient patient adherence to medication often results in unsatisfactory treatment outcomes, increasing both the recurrence and rehospitalization rates of depression, and consequently imposing a greater economic burden on the healthcare system. Objectives Our objective was to examine the impact of pharmacogenomic testing on medication adherence and antidepressant switching rates among individuals diagnosed with depression. Methods This retrospective cohort study encompassed patients diagnosed with depression who were admitted to the First Hospital of Hebei Medical University between April 2022 and September 2023. Patients were categorized into a pharmacogenomics-guided treatment (PGxT) group and a treatment as usual (TAU) group based on whether pharmacogenetic testing was conducted. The primary outcome measures included the proportion of patients exhibiting medication adherence greater than 80% at three and 6 months post-discharge, as well as the proportion of patients experiencing changes in their prescribed medication types. Results A total of 310 patients in the PGxT group and TAU group were obtained through propensity score matching. Among the 620 patients in both groups, 57.42% demonstrated good adherence (≥80%) at 3 months; this percentage dropped to 31.45% at 6 months. At 3 months of observation, the percentages of patients demonstrating good adherence were significantly different between the groups (64.52% in the PGxT group vs. 50.32% in the TAU group; p < 0.001). The difference was also significant after 6 months (38.06% in the PGxT group vs. 24.84% in the TAU group; p < 0.001). Furthermore, patients receiving PGxT (20.64%) exhibited a lower rate of antidepressant conversion compared to those receiving TAU (31.29%). Conclusion The findings of this study indicate that pharmacogenomics testing positively influences treatment adherence and may decrease the need to switch medications among patients with depression.

Background Intranasal administration is a convenient route for drug delivery that can be applied for procedural sedation. However, there is currently limited exploration into fixed dosing regimens. This study was to investigate the pharmacokinetics (PK), pharmacodynamics (PD), bioavailability (BA) and safety of dexmedetomidine after fixed doses of intranasal and intravenous administration in healthy male and female subjects. Methods Group A subjects received intranasal or intravenous administration in two periods (12 subjects received intranasal dexmedetomidine (Dex) or the intravenous formulation, and four received the corresponding placebo). Groups B to F underwent single-period dose ascending, receiving only the intranasal Dex formulation or the corresponding placebo (the number of subjects receiving the drug/placebo in groups B to F were 12/2, 12/2, 12/2, 10/2, 10/2, respectively), with doses of 75 μg, 125 μg, 150 μg, 175 μg, and 200 μg, respectively. After administration of each group, blood samples were collected to investigate the plasma concentration of dexmedetomidine, adrenaline and noradrenaline using a HPLC-MS/MS method. Ramsay score, blood pressure and heart rate were collected for safety evaluation. Pharmacokinetic parameters (C max , T max , AUC 0-24h , AUC 0 – ∞ , and t 1/2 ) of dexmedetomidine were calculated. Results A total of 82 subjects were randomized. One subject withdrew for personal reasons before administration and the other subjects completed the entire study process. At a dose of 25 μg, the absolute bioavailability was 59%. Across the dose range of 25 to 200 μg, the median T max was similar (0.5–1 h), and the mean elimination half-life was comparable (3.09–4.28 h), with exposure (C max and AUC 0-t ) increasing with dose. The pharmacokinetics after intranasal spray administration exhibited linear characteristics, although C max was similar in the higher dose groups (175 μg and 200 μg). PD results showed that ideal sedation effects (Ramsay score of 3 or higher in at least 90% of subjects) could be achieved within 30 min following intranasal administration of 75 μg or higher doses. All the subjects were well tolerated without any serious adverse events (SAEs). Conclusion Dexmedetomidine nasal spray was well tolerated and achieved satisfactory sedation in the dose range of 25–200 μg in Chinese healthy male and female subjects. Clinical Trial Registration http://www.chinadrugtrials.org.cn/ , identifier CTR20201650

Alcohol-related liver disease (ALD) is a major cause of morbidity and mortality worldwide. It encompasses conditions such as fatty liver, alcoholic hepatitis, chronic hepatitis with liver fibrosis or cirrhosis, and hepatocellular carcinoma. Numerous recent studies have demonstrated the critical role of oxidative stress, abnormal lipid metabolism, endoplasmic reticulum stress, various forms of cell death (including apoptosis, necroptosis, and ferroptosis), intestinal microbiota dysbiosis, liver immune response, cell autophagy, and epigenetic abnormalities in the pathogenesis of ALD. Currently, abstinence, corticosteroids, and nutritional therapy are the traditional therapeutic interventions for ALD. Emerging therapies for ALD mainly include the blockade of inflammatory pathways, the promotion of liver regeneration, and the restoration of normal microbiota. Summarizing the advances in animal models of ALD will facilitate a more systematic investigation of the pathogenesis of ALD and the exploration of therapeutic targets. This review summarizes the latest insight into the pathogenesis and molecular mechanisms of ALD, as well as the pros and cons of ALD rodent models, providing a basis for further research on therapeutic strategies for ALD.

We report a case of an advanced non-small cell lung cancer (NSCLC) patient with brain metastasis, RET fusion, and high expression of programmed death ligand 1 (PD-L1) at initial treatment. After receiving radiotherapy for the brain metastasis, the patient started with anlotinib and added immunotherapy with sintilimab. The patient had a good response to anlotinib and sintilimab treatment, tolerated the adverse reactions, and had a progression-free survival (PFS) of over 17 months. To the best of our knowledge, this is the first clinical case report in the literature describing the benefit of anlotinib and sintilimab treatment for non-small cell lung cancer with RET fusion and high PD-L1 expression. This study explores the biomarker selection for targeted therapy and combined immunotherapy in NSCLC patients.

Background Ubiquitin-specific peptidases (USPs), also known as deubiquitinating enzymes (DUBs), play a crucial role in maintaining cellular homeostasis by selectively removing ubiquitin molecules from targeted proteins. This process affects protein stability, subcellular localization, and activity, thereby influencing processes such as DNA repair, cell cycle regulation, and apoptosis. Abnormal USP activities have been linked to various diseases, including cancer. Emerging evidence in lymphoma studies highlights the significance of USPs in controlling signaling pathways related to cancer initiation and progression and presents them as potential therapeutic targets. Aim This study aimed to elucidate the multifaceted roles of USPs in lymphoma. Methods This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published in English up to May 2023 were retrieved from PubMed, Web of Science, and Scopus. The inclusion criteria focused on studies investigating the role of USPs in lymphoma cancer, involving human subjects or relevant lymphoma cell lines, exploring molecular mechanisms and signaling pathways, and assessing diagnostic or prognostic value. Results After the selection process, 23 studies were selected for analysis. USPs were found to affect various aspects of lymphoma development and progression. Specific USPs were identified with roles in cell-cycle regulation, apoptosis modulation, drug resistance, DNA repair, and influence of key oncogenic pathways, such as B cell receptor (BCR) signaling. Conclusion This systematic review underscores the emerging role of USPs in lymphoma and their potential as therapeutic targets. Inhibitors of USPs, such as USP14 inhibitors, show promise in overcoming drug resistance. The dynamic interplay between USPs and lymphoma biology presents an exciting opportunity for future research and the development of more effective treatments for patients with lymphoma. Understanding the intricate functions of USPs in lymphoma offers new insights into potential therapeutic strategies, emphasizing the significance of these enzymes in the context of cancer biology.

Disproportionality analyses are the most-commonly used study design used in the post-marketing phase to detect suspected adverse drug reactions in individual case safety reports. Recent years have witnessed an exponential increase in published articles on disproportionality analyses, thanks to publicly accessible databases. Unfortunately, this trend was accompanied by concerns on lack of transparency and misinterpretation of results, both generating unjustified alarm and diluting true signals into overwhelming noise. The READUS-PV guideline for reporting disproportionality analysis was developed to tackle this emerging issue. In this perspective article, we describe the rationale behind the development of the READUS-PV guideline, the first collaborative initiative to harmonize the reporting of disproportionality analyses. The adoption of the checklists will assist researchers, regulators, and reviewers in the reporting, assessment, and publication of disproportionality analyses. Acknowledging the challenges ahead of effective implementation, we advocate for a global endorsement by Pharmacology Journals. A wide dissemination of the READUS-PV guideline is crucial to foster transparency and reproducibility of pharmacovigilance research, supporting an effective exploitation of disproportionality analysis among other irreplaceable post-marketing research tools to ensure drug safety.

Introduction Cannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects. Methods Herein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells. Results Two CBD piperazinyl derivatives ( 19 and 21 ) showed augmented antiproliferative effects with an IC 50 of 5.5 and 4.1 µM, respectively, compared to CBD’s IC 50 of 22.9 µM. Further studies suggest that modulation of apoptosis and ferroptosis may contribute to the cytotoxic effects of CBD and its derivatives. In addition, CBD and its derivatives ( 19 and 21 ) were explored for their potential synergistic antiproliferative effects in combination with chemotherapeutic agent cisplatin. Compounds 19 or 21 (5 µM) combined with cisplatin (1 µM) showed a synergistic effect with a combination index of 0.23 and 0.72, respectively. This effect was supported by elevated levels of reactive oxygen species in Caov-3 cells treated with cisplatin combined with 19 or 21 . Discussion Findings from this study suggest that CBD derivatives with enhanced antiproliferative effects may exert synergistic effects with chemotherapeutic drugs, providing insight into the development of cannabinoid-based adjuvant agents for the management of ovarian cancer.

Aim To explore the molecular mechanism of Sijunzi Decoction (SJZD) in the treatment of Parkinson’s disease (PD) through the application of network pharmacology, molecular docking, and molecular dynamics simulations, complemented by experimental verification. Methods The BATMAN-TCM, GeneCards, and DisGeNet databases were searched to screen the active components and therapeutic targets of SJZD. Cytoscape (3.7.1) was used to create a network diagram of the components and targets. The STRING platform was used to construct a protein-protein interaction (PPI) network. The Bioconductor database and RX64 (4.0.0) software were used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the core target genes. The binding sites and binding energies between SJZD active components and the target were analyzed by molecular docking and dynamic simulation. Finally, the therapeutic effect and mechanism of SJZD were verified by Cell Counting Kit-8 (CCK-8) and Western blotting (WB). Results This research identified 188 active compounds in SJZD, 1568 drug targets, 2069 PD targets, and 451 intersection targets related to PD. According to network analysis, Adenosine Triphosphate, Tridecanoic Acid, Hexadecanoic Acid, Pentadecanoic Acid, and Adenosine were identified as the core components of SJZD in the treatment of PD. The five targets with the highest Degree values in the PPI network were AKT1, INS, TNF, IL-6, and TP53. The GO and KEGG enrichment analyses, in turn, determined that the administration of SJZD for the treatment of PD may engage processes such as xenobiotic stimulation and biological stimulus response. Furthermore, AGE-RAGE and cAMP signaling pathways related to diabetic complications may be involved. Molecular docking and kinetic simulations showed that IL-6 and AKT1 bind best to Adenosine. Experimental results showed that SJZD significantly reduced 6-OHDA-induced apoptosis of SH⁃SY5Y cells by activating the PI3K/AKT signaling pathway and regulating the expression of apoptosis factors such as Bcl⁃2 and Bax. Conclusion SJZD is essential in the processes of apoptosis and neuronal protection, acting through various components that target multiple pathways. Notably, the PI3K/AKT pathway is a verified SJZD-PD target, providing a reference for clinical precision drug use for PD.

To explore the correlation of the DRD2 gene polymorphism with psychopathology and predict responses in patients with mania treated with lithium and olanzapine. Sixty patients with bipolar mania were treated with lithium combined with olanzapine for 8 weeks and assessed using YMRS, HAMD, and HAMA. The DRD2 gene polymorphism rs1800497 was tested. Eleven (24.4%) manic patients achieved an early effective response according to the reduction of the YMRS score of >20% in the 2nd week, with a lower HAMA score than the no early effective response group. Twenty-three (51.1%) manic patients achieved remission according to the reduction of the YMRS score of >75% at the 8th week with a higher dose of lithium at the 8th weekend (g/day) than in the no-remission group. Manic patients with genotype GG had lower YMRS scores and lower doses and serum concentrations of olanzapine than patients with genotype AA + AG from the 4th week to the 8th week. Manic patients with genotype GG had a higher relative change in the YMRS score than those with genotype AA + AG from the 2nd week to the 8th week. No differences in HAMA or HAMD were found between the groups with genotype GG and AA + AG. There were more patients who achieved an early effective response in the 2nd week and remission in the 8th in those with genotype GG compared to those with genotype AA + AG. Manic patients with genotype GG had a greater improvement in the YMRS score due to a greater early effective response and remission, which was not related to higher doses and serum concentrations of olanzapine and lithium.

Background This study aims to improve the solubility and the toxicity of Bufonis venenum, and finally enhance the therapeutic outcomes of hepatocellular carcinoma (HCC). Methods The cholesterol-free liposomes simultaneously encapsulate bufadienolides and indolealkylamines (Non-Cholesterol-Bufonis Venenum Extract-Liposome, Non-Chol-BVE-LP) was prepared by the thin-film evaporation technique. In vitro , the cytotoxicity, cell apoptosis study, cellular uptake and hemolysis studies were evaluated in HepG2 cells. In vivo , the biodistribution and anti-tumor activity studies were conducted in BALB/C mice with HepG2 cells. Results The liposomes showed good size distribution, encapsulation efficiency drug loading capacity and slower drug release. Non-Chol-BVE-LP had higher cytotoxicity on HepG2 cells and induced more apoptosis on HepG2 Cells compared with BVE. In addition, the liposomes could accumulate in tumor by passive targeting, thus facilitating the anti-tumor effects. In vivo , Non-Chol-BVE-LP showed equivalent anti-tumor efficacy to the first-line anti-HCC drug sorafenib. Conclusion The study provided new ideas for the development and clinical application of Bufonis venenum related formulation and offered new drug for the treatment of HCC.

Introduction Neuropathic pain is a debilitating neurological disorder and is on the rise. Since no effective treatment has been so far approved to combat the complex pathological mechanisms behind neuropathic pain, finding new therapeutic candidates is of great importance. Astaxanthin (AST) is a carotenoid with strong antioxidant, and anti-inflammatory activities. Purpose The present research aimed to evaluate the ameliorative effects of AST on a rat model of neuropathic pain. Methods To induce neuropathic pain, a chronic constriction injury (CCI) model was employed. Accordingly, Wistar rats were divided into nine groups of six including sham, negative control group (CCI), positive control group gabapentin (100 mg/kg), AST (5, 10 mg/kg), flumazenil (0.5 mg/kg), naloxone (0.1 mg/kg), AST (10 mg/kg) + flumazenil (0.5 mg/kg), and AST (10 mg/kg) + naloxone (0.1 mg/kg) were administered intraperitoneally on days 1, 3, 5, 7, 10, and 14. To check the experimental signs of neuropathic pain and motor dysfunction, hot plate, acetone drop, and open field tests were used at the same time points. Additionally, biochemical assay and zymography were done on days 7 and 14 to assess the changes in catalase, glutathione and nitrite, as well as matrix metalloproteinases (MMP-2 and MMP-9). Besides, histological evaluations were performed for tissue damages on days 7 and 14. Results and discussion Results indicated that intraperitoneal injection of AST improved allodynia, hyperalgesia, and locomotor activity after CCI. AST also increased catalase and glutathione while suppressing nitrite, MMP-2, and MMP-9 activity through opioid/benzodiazepine receptors. Conclusion The results highlighted AST as a promising candidate against neuropathic pain with beneficial effects on motor function by suppressing inflammatory mediators, and augmenting antioxidant factors, passing through opioid/benzodiazepine receptors.

Scutellaria baicalensis has been used for the treatment of digestive system disorders for thousands of years in China and other regions. Modern research have revealed its therapeutic efforts in digestive system tumors. Thus, to review the updated progress of S. baicalensis and its main flavonoids in the treatment of digestive system tumors in the past 10 years, this article summarized the therapeutic effect and molecular mechanisms of S. baicalensis and its 5 flavonoids on tumors in oral cavity, esophagus, stomach, colon, liver, pancreas by inhibiting tumor cell proliferation, inducing autophagy, stimulating immune response, and increasing drug sensitivity. In conclusion, S. baicalensis and its flavonoids could be applied to treat digestive system tumors with different type of methods.

Background A growing body of research is dedicated to developing new therapeutic agents for wound healing with fewer adverse effects. One of the proceedings being taken today in wound healing research is to identify promising biological materials that not only heal wounds but also vanish scarring. The effectiveness of nanofibers like polyvinyl alcohol (PVA), in improving wound healing can be related to their unique properties. Pistacia atlantica Desf. subsp. kurdica (Zohary) Rech. f. ( PAK ) [Anacardiaceae], also known as “Baneh” in traditional Iranian medicine, is one of the most effective herbal remedies for the treatment of different diseases like skin injuries due to its numerous pharmacological and biological properties, including anti-inflammatory, antioxidant, and anti-bacterial effects. Purpose Our study aimed to evaluate the wound-healing activity of nanofibers containing PVA/ PAK oleo-gum-resin in two rat models of burn and excision wound repair. Material and Methods PVA/ PKA nanofibers were prepared using the electrospinning method. Scanning electron microscope (SEM) images and mechanical properties of nanofibers were explored. Diffusion and releasing experiments of nanofibers were performed by the UV visible method at different time intervals and up to 72 h. The animal models were induced by excision and burn in Wistar rat’s skin and the wound surface area was measured during the experiment for 10 and 21 days, respectively. On the last day, the wound tissue was removed for histological studies, and serum oxidative factors were measured to evaluate the antioxidant properties of the PVA/ PKA . Data analysis was performed using ImageJ, Expert Design, and statistical analysis methods. Results and discussion PVA/ PKA nanofibers were electrospun at different voltages (15, 18, and 20 kV). The most suitable fibers were obtained when the nozzle was positioned 15 cm away from the collector, with a working voltage of 15 kV, and an injection rate of 0.5 mm per hour, using the 30:70 w/v PKA gum. In the SEM images, it was found that the surface tension of the polymer solution decreased by adding the gum and yield thinner and longer fibers at a voltage of 15 kV with an average diameter of 96 ± 24 nm. The mechanical properties of PVA/ PKA nanofibers showed that the presence of gum increased the tensile strength and decreased the tensile strength of the fibers simultaneously. In vivo results showed that PVA/ PKA nanofibers led to a significant reduction in wound size and tissue damage (regeneration of the epidermal layer, higher density of dermal collagen fibers, and lower presence of inflammatory cells) compared to the positive (phenytoin and silver sulfadiazine) and negative control (untreated) groups. Wound contraction was higher in rats treated with PVA/ PKA nanofibers. Additionally, antioxidative serum levels of catalase and glutathione were higher in the PVA/ PKA nanofiber groups even in comparison to positive control groups. Conclusion Pistacia atlantica oleo-gum-resin-loaded electrospun nanofibers potentially improve excision and burn models of skin scars in rats through antioxidative and tissue regeneration mechanisms.

Dietary restriction (DR) has long been recognized as a powerful intervention for extending lifespan and improving metabolic health across species. In laboratory animals, DR—typically a 30%–40% reduction in caloric intake—delays aging and enhances mitochondrial function, oxidative defense, and anti-inflammatory pathways. In humans, findings from the CALERIE™ trial confirm DR’s potential benefits, with a 25% caloric reduction over 2 years resulting in reduced visceral fat, improved cardiometabolic health, and favorable gene expression changes linked to proteostasis, DNA repair, and inflammation. However, recent research in genetically diverse mouse populations reveals that the impact of DR on lifespan is substantially modulated by genetic background, underscoring the importance of individual variability. Additionally, emerging evidence challenges previous assumptions that lower body temperature universally benefits lifespan extension, with data indicating complex relationships between thermoregulation, sex, and longevity. These findings underscore the need for nuanced approaches to DR in both research and potential therapeutic applications, with considerations for genetic and sex-specific factors to maximize healthspan and lifespan outcomes.

Introduction Endothelial cell (EC) calcification is an important marker of atherosclerotic calcification. ECs play a critical role not only in atherogenesis but also in intimal calcification, as they have been postulated to serve as a source of osteoprogenitor cells that initiate this process. While the role of transglutaminase 2 (TG2) in cellular differentiation, survival, apoptosis, autophagy, and cell adhesion is well established, the mechanism underlying the TG2-mediated regulation of EC calcification is yet to be fully elucidated. Methods The TG2 gene was overexpressed or silenced by using siRNA and recombinant adenovirus. RT-PCR and WB were used to analyze the relative expression of target genes and proteins. 5-BP method analyzed TG2 activity. mCherry-eGFP-LC3 adenovirus and transmission electron microscopy analyzed EC autophagy level. Calcium concentrations were measured by using a calcium colorimetric assay kit. Alizarin red S staining assay analyzed EC calcification level. Elisa analyzed IL-6 level. Establishing EC calcification model by using a calcification medium (CM). Results Our findings demonstrated that CM increased TG2 activity and expression, which activated the NF-κB signaling pathway, and induced IL-6 autocrine signaling in ECs. Furthermore, IL-6 activated the JAK2/STAT3 signaling pathway to suppress cell autophagy and promoted ECs calcification. Discussion ECs are not only critical for atherogenesis but also believed to be a source of osteoprogenitor cells that initiate intimal calcification. Previous research has shown that TG2 plays an important role in the development of VC, but the mechanism by which it exerts this effect is not yet fully understood. Our results demonstrated that TG2 forms complexes with NF-κB components inhibition of autophagy promoted endothelial cell calcification through EndMT. Therefore, our research investigated the molecular mechanism of EC calcification, which can provide new insights into the pathogenesis of atherosclerosis.