Jamia Hamdard University

Peptides are functional biomolecules that hold great potential for the discovery of new therapeutics and drug delivery systems. Structurally, these are short molecules, but they possess similar functionality of large proteins. Peptides can overcome the physiological barriers posed by the diseases due to their intrinsic properties. In recent years, bioactive peptides such as antimicrobial, anticancer, antithrombotic, antidiabetic, and anti-Alzheimer effects have been successfully identified, and many of them are in clinical trials. Apart from that, peptides are also reported for the drug delivery applications as targeting molecules or as self-assembling soft nano-materials. This chapter offers a brief introduction to peptides as therapeutics and drug delivery agents and their application in the management of different diseases through targeted therapy. Here, we discuss the recent development on peptides as carriers to penetrate different physiological barriers such as gastrointestinal (GI) tract and blood-brain barriers.

In the present study, multigrain fermented noodles were prepared using seera (fermented wheat starch), green gram, sorghum, and finger millet flours with different proportions. Then, the optimized formulation was developed, and cooking characteristics, sensory attributes, nutritional composition, and in vitro protein digestibility (IVPD) were evaluated. The prepared noodles showed better cooking characteristics, sensory attributes, and overall acceptability. Compared to commercial and control noodles, the optimized multigrain fermented noodles exhibited higher fiber, total phenol content, ash, iron, reducing sugar, and protein content. At the same time, the IVPD ( 92.5 ± 0.29 % ) of multigrain fermented noodles was comparable to control as well as commercial noodles. The XRD pattern showed a sharp peak at 15 and 20°, and the overall crystallinity was 34.12% observed. The ready-to-cook multigrain fermented noodles, prepared from the fermented wheat starch base, can be used as a healthy choice to refine wheat flour-based noodles, reducing chronic diseases.

Alzheimer’s disease (AD) and brain tumors are debilitating neurological conditions that pose significant challenges in current medical practices. Existing treatment options for AD primarily focus on symptom management, and brain tumors often require aggressive therapeutic approaches. Novel disease-modifying strategies and therapeutic agents are urgently needed to address the underlying causes of AD pathogenesis and improve brain tumor management. In recent years, nanoparticles (NPs) have shown promise as valuable tools in diagnosing and managing various brain disorders, including AD. Among these, carbon nanotubes (CNTs) have garnered attention for their unique properties and biomedical potential. Their ability to cross the blood-brain barrier (BBB) with ease opens up new possibilities for targeted drug delivery and neuroprotection. This literature review aims to explore the versatile nature of CNTs, which can be functionalized with various biomolecules or substances due to their sp2 hybridization. This adaptability enables them to specifically target cells and deliver medications under specific environmental conditions. Moreover, CNTs possess an exceptional capacity to penetrate cell membranes, making them valuable tools in the treatment of AD and brain tumors. By delving into the role of CNTs in biomedicine, this review sheds light on their potential in managing AD, offering a glimpse of hope for effective disease-modifying options. Understanding the mechanisms of CNTs’ action and their capabilities in targeting and delivering medication to affected cells will pave the way for innovative therapeutic strategies that can improve the lives of those afflicted with these devastating neurological conditions. The exploration of CNTs as a dual therapeutic arsenal for both brain tumors and Alzheimer’s disease holds great promise and may usher in a new era of effective treatment strategies for these challenging conditions.

Digitalization contains a diverse set of information that plays a vital role in investigations, from a forensic stand point. Forensic investigations in the IoT/digital paradigms will need to develop and mature in order to meet the characteristics of IoT. In this paper the authors have investigated digital forensics and have addressed the method of processing the sources of evidences in the digital/IoT ecosystem. The authors have further outlined the guidelines, procedures, current trends and a few criteria and roadblocks in the process of digital investigation. This study lays open ways for investigating strategies and methodologies which support the implementation of digital forensics in the dynamic digital systems. This provides a deep and detailed comprehensive understanding of digital forensics and IoT forensics. Further, current problems and issues are highlighted which will inspire and motivate researchers for further research.

Artificial intelligence and machine learning are expanding day by day virtual assistant bots, also known as chatbots are one of the many new technologies that will continue to touch our daily lives. A healthy lifestyle depends heavily on proper healthcare. Nevertheless, it might be exceedingly challenging to schedule a doctor’s appointment for every health issue. The goal is to develop a medical chatbot utilizing artificial intelligence that can diagnose the disease and provide precaution about it. It helps you to reduce the healthcare cost, also saves your time, and improves accessibility to medical knowledge. In recent years, numerous businesses and organizations have partnered with hospitals to offer assistance that can help doctors and medical personnels deal with patients better and expend less energy thanks to technology, chatbots have a lot of potential to transform the healthcare sector. With the aid of a text diagnosis bot, patients can participate in drug reviews and give a unique analysis report based on their symptoms. People will therefore be aware of their health and be properly protected. Certain chatbots serve as medical encyclopedias, educating patients about their conditions and promoting better health. A chatbot based on Sklearn is where you can give a symptom and it will ask you questions and will tell you the details and give some advice. This research study utilized “train test split” (split arrays into random train and test subsets) and “cross Val score” (evaluate a score by cross-validation) modules from Sklearn, Sklearn SVC (support vector classification). In this paper, authors have trained our model based on given data we gathered from the Internet (check data folder) and used Sklearn decision tree classifier (DTC). In multi-label classification, this is the subset accuracy which is a harsh metric since you require for each sample that each label set is correctly predicted.

The plant growth regulator, jasmonic acid (JA) has emerged as important molecule and involved in key processes of plants. In this study, we investigated the role of methyl jasmonate (MeJA) in achieving tolerance mechanisms against arsenic (As) stress in rice (Oryza sativa). Arsenic toxicity is a major global concern that significantly deteriorate rice production. The application of MeJA (20 μM) and ethylene (150 μL L-1) both individually and/or in combination were found significant in protecting against As-induced toxicity in rice, and significantly improved defense systems. The study shown that the positive influence of MeJA in promoting carbohydrate metabolism, photosynthesis and growth under As stress were the result of its interplay with ethylene biosynthesis and reduced oxidative stress-mediated cellular injuries and cell deaths. Interestingly, the use of JA biosynthesis inhibitor, neomycin (Neo) and ethylene biosynthesis inhibitor, aminoethoxyvinylglycine (AVG) overturned the effects of MeJA and ethylene on plant growth under As stress. From the pooled data, it may also be concluded that Neo treatment to MeJA- treated rice plants restricted JA-mediated responses, implying that application of MeJA modulated ethylene- dependent pathways in response to As stress. Thus, the action of MeJA in As tolerance is found to be mediated by ethylene. The study will shed light on the mechanisms that could be used to ensure the sustainability of rice plants under As stress.

Etravirine (ERVN) is a potential NNRTI (non-nucleoside reverse transcriptase inhibitor) in treating HIV infection. It possesses extremely low oral bioavailability. The present research aims to optimize the formulation and characterization of TPGS-enriched ERVN-loaded lipid-based nanocarriers (LNCs) for HIV-infected patients. The formulation, ERVN-TPGS-LNCs, was optimized by CCRD using a modified-solvent evaporation process. Various characterization parameters of LNCs were evaluated, including globule size of 121.56 ± 2.174 nm, PDI of 0.172 ± 0.042, the zeta potential of -7.32 ± 0.021 mV, %EE of 94.42 ± 8.65% of ETR and %DL was 8.94 ± 0.759% of ERVN and spherical shape was revealed by TEM. PXRD was also performed to identify the crystallinity of the sample. In-vitro drug release showed % a cumulative drug release of 79.77 ± 8.35% at pH 1.2 and 83.23 ± 9.11% at pH 6.8, respectively, at the end of 48h compared to pure drug suspension (ERVN-S). Further, the intestinal permeation study and confocal microscope showed approximately ~3-fold and ~2-fold increased permeation in ERVN-TPGS-LNCs and ERVN-LNCs across the gut sac compared to ERVN-S. Hemolysis compatibility and lipolysis studies were performed to predict the in-vivo fate of the formulation. The pharmacokinetic study revealed a 3.13-fold increment in the relative bioavailability, which agrees with the ex-vivo studies, and lymphatic uptake was validated by using cycloheximide (CYHD) along with designed formulation, which leads to lowering AUC of ERVN-TPGS-LNCs. Thus, this study ensures that ERVN-TPGS-LNCs take lymphatic uptake to minimize the first-pass metabolism followed by improved oral bioavailability of EVN. Thus, the enhanced bioavailability of ERVN can reduce the high dose of ERVN to minimize the adverse effects related to dose-related burden.

Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4+ and CD8+ T cells, CD14+ monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.

With their distinctive core–shell design, core–shell nanocrystals have drawn interest in catalysis, medicinal research, and nanotechnology. These nanocrystals have a variety of characteristics and possible uses. The application of core–shell nanocrystals offers significant potential in increasing diagnostic and therapeutic approaches for cancer research in apoptosis and in vitro cancer cell imaging. In the present study, we investigated the fluorescence behavior of hydrophilic CdSe (core-only) and CdSe@CdS (core–shell) nanocrystals (NCs) and their potential in cancer cell imaging. The addition of a CdS coating to CdSe NCs increased the fluorescence intensity tenfold. The successful fabrication of core–shell CdSe@CdS nanocrystals was proven by a larger particle size (evaluated via DLS and TEM) and their XRD pattern and surface morphology compared to CdSe (core-only) NCs. When these NCs were used for bioimaging in MCF-7 and HEK-293 cell lines, they demonstrated excellent cellular uptake due to higher fluorescence intensity within cancerous cells than normal cells. Comparative cytotoxicity studies revealed that CdSe NCs were more toxic to all three cell lines (HEK-293, MCF-7, and HeLa) than CdSe@CdS core–shell structures. Furthermore, a decrease in mitochondrial membrane potential and intracellular ROS production supported NCs inducing oxidative stress, which led to apoptosis via the mitochondria-mediated pathway. Increased cytochrome c levels, regulation of pro-apoptotic gene expression (e.g., p53, Bax), and down-regulation of Bcl-2 all suggested cellular apoptosis occurred via the intrinsic pathway. Significantly, at an equivalent dose of core–shell NCs, core-only NCs induced more oxidative stress, resulting in increased apoptosis. These findings shed light on the role of a CdS surface coating in reducing free radical release, decreasing cytotoxicity, and improving fluorescence, advancing the field of cell imaging.

Autism spectrum disorder (ASD) is a developmental disorder that causes difficulty while socializing and communicating and the performance of stereotyped behavior. ASD is thought to have a variety of causes when accompanied by genetic disorders and environmental variables together, resulting in abnormalities in the brain. A steep rise in ASD has been seen regardless of the numerous behavioral and pharmaceutical therapeutic techniques. Therefore, using complementary and alternative therapies to treat autism could be very significant. Thus, this review is completely focused on non-pharmacological therapeutic interventions which include different diets, supplements, antioxidants, hormones, vitamins and minerals to manage ASD. Additionally, we also focus on complementary and alternative medicine (CAM) therapies, herbal remedies, camel milk and cannabiodiol. Additionally, we concentrate on how palatable phytonutrients provide a fresh glimmer of hope in this situation. Moreover, in addition to phytochemicals/nutraceuticals, it also focuses on various microbiomes, i.e., gut, oral, and vaginal. Therefore, the current comprehensive review opens a new avenue for managing autistic patients through non-pharmacological intervention.

Introduction Inflammation is the first response and an alarming signal for the onset of chronic disease. Most of the anti-inflammatory drugs available in the market are reported to have undesirable gastrointestinal toxicities. Therefore, it is of urgent significance to develop anti-inflammatory drugs with low toxicity and good efficacy. METHOD We created a targeted scaffold based on a literature review by combining the different structural characteristics of furan and benzyl amides into a single pharmacophore. A series of eighteen furan-based derivatives (1-18) were designed, synthesized for in-vitro and in-vivo anti-inflammatory activity. The characterization of synthesized compounds was elucidated by techniques like 1H-NMR, 13C-NMR, FT-IR and MS. Result The synthetic compounds were examined through molecular docking studies on TNF-α for probable binding mode and interactions with hydrophilic and hydrophobic pocket of TNF-α in comparison to standard drug (Indomethacin). Conclusion When compared to the standard treatment, compounds 18, 15 and 9 displayed a remarkable inhibitory effect on the production of TNF-α and in-vivo inflammatory activity with no damage to stomach and reduction of LPO. The compounds 18, 15 and 9 might be a good consideration for potential anti-inflammatory agents.

A series of novel thiosemicarbazone derivatives containing 5-methoxy isatin were designed and synthesized with modification on N(4) position. Derivatives considering structure-activity relationship have been designed and synthesized by condensing thiosemicarbazide with 5-methoxy isatin. The synthesized compounds were characterized by elemental analysis, FT-IR spectroscopy, UV-visible spectroscopy, NMR (1H, 13C) spectroscopy, mass spectrometry, and a single-crystal study. Biological evaluation of the synthesized compounds revealed that MeOIstPyrd is the most promising compound against skin cancer cell line, A431, with an IC50 value of 0.9 μM. In addition, MeOIstPyrd also exhibited low toxicity against the normal human fibroblast and the human embryonic kidney 293 cell line, HLF-1, and HEK293, respectively. Furthermore, the mechanistic study revealed that MeOIstPyrd efficiently inhibited cell proliferation, migration, and spheroid formation by activating the mitochondrial intrinsic apoptotic pathway. MeOIstPyrd also induces DNA damage and activates p53 irrespective of the p53 status. It increases the half-life of p53 and stabilizes p53 by phosphorylating it at ser15. Moreover, MeOIstPyrd was found to bind to MDM2 in the p53 sub-pocket and, therefore, block p53-MDM2 interaction. Our result exhibited potential anticancer activity of MeOIstPyrd in the A431 cell line and its ability in restoring mutant p53, which is an interesting and promising strategy for cancer therapeutics.

The present study aimed to assess the pharmacological mechanism of Salvia officinalis in Neurodegenerative disorders using a network pharmacology approach followed by molecular docking analysis. Phytoconstituents of S.officinalis were obtained from various databases, followed by the screening of active ingredients using the Swiss ADME web tool. Potential targets of active ingredients were identified using PubChem & SwissTargetPrediction. Genes related to Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) were gathered using online databases. Besides, the correlation between active ingredient targets and disease-associated genes was linked. Networks were constructed, visualized, and analyzed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis were performed using DAVID database. Decisively, Autodock was used for molecular docking. The results of network analysis identified 9 key active ingredients based on topological analysis of the active ingredient - candidate targets network. Also, the analysis revealed a shared target of 9 key active ingredients of S. officinalis that interacted with 133 AD-related targets whereas only 6 active ingredients interacted with 85 and 58 targets of PD and HD respectively. The core genes from the network were AKT1, BACE1, CASP3, MAPK1, TNF, and IL6. Furthermore, GO and KEGG enrichment analysis showed that FOXO, TNF, MAPK, PI3K-Akt, Rap 1, and neurotrophin signalling pathways as enriched, which were further validated by molecular docking suggesting the protective role of S. officinalis in neurodegenerative diseases. Our research reveals the therapeutic benefits of S. officinalis , which might play a crucial role in modulating neurodegenerative diseases.

Donepezil hydrochloride (DPL) and Embelin (EMB) loaded Nanostructured Lipid Carriers (NLCs) have been developed and optimized to achieve optimal drug loading, safer nasal delivery, effective neuronal/cell uptake, enhanced brain accessibility, controlled release, and desired therapeutic effect. Molecular docking studies demonstrated that both drugs bind effectively to AchE with interaction energies of -48.5319 and − 65.7525, respectively, indicating a synergistic approach. The hydrophobic interactions with target proteins facilitate the transportation of drugs through brain hydrophobic channels to provide a desired pharmacological response. N2a cell line investigation advised a 1:1 ratio of DPL and EMB to have the greatest possible synergistic effect based on the MTT assay. NLCs were fabricated by hot emulsification probe sonication method and optimized using QbD-based Central Composite Rotatable Design (CCRD). Optimized NLCs with a diameter of 180.2 nm were suitable for axonal uptake. A low PDI score of 0.37 and ZP of -12 mV indicated a uniform monodisperse system with persistent and stable dispersion properties. The NLCs demonstrated sustained drug release, DPL released at 90.72 ± 1.00 percent and EMB at 81.30 ± 0.52 percent in 24 hours. The Korsemeyer-Peppas model proved to be the most accurate fit due to its strong correlation. Ex vivo permeation and CLSM studies revealed superior goat nasal mucosa penetration of NLCs over suspension with a higher fluorescence level, up to 35 µm. NLCs treated nasal mucosa exhibited no erosion or interstitial gaps in the histopathological study. Moreover, NLCs were nontoxic and non-irritating, with a HET CAM score of 0.68 ± 0.05, indicating safe nasal delivery. The cellular uptake study showed a preponderance of the NLCs in the Cell's cytoplasm, indicating ready uptake by N2a cells. Hence, intranasal therapy with the DPL and EMB-loaded NLCs could be a practical and promising implementation. Further in vivo , and clinical studies will be required to establish the formulation's efficacy in treating Alzheimer’s disease (AD).

NMDAR (N-methyl-D-aspartate receptor) antagonist and opioid agonist can induce psychosis in rodents and humans. Loperamide hydrochloride (LH) possesses NMDAR antagonistic and opioid agonistic property but associated with more peripheral effects and limited blood brain barrier (BBB) penetration. So, it is essential to make its nanoformulation to increase BBB penetration and reduce peripheral effects. Thus, this study aimed to develop of LH encapsulated tween 80 coated chitosan nanoformulations and to optimize the formulations for targeting into brain. 3² full factorial design was performed to optimize the preparation to enhance the entrapment of the drug and reduce the particle size of all batches were between 189–278 nm and 80.16–89.38%, respectively. Pure drug LH (1 mg/kg, p.o) and LH loaded tween 80 coating chitosan nanoparticles (LCNP) (dose equal to 1 mg/kg LH, p.o.) were administrated in different group of animals to produce psychosis like behaviors in terms of stereotypic behaviors, hyper-locomotors activity, immobility and increased step down latency. LH and LCNP were administered orally for 15 successive days and behavioral, biochemical and histopathological alterations were studies. In mice, LCNP administration showed to induced behavioral changes similar to psychotic symptoms. However, administration of LH didn’t shows significant effect in cognitive symptom. Moreover, LCNP significantly decreased GSH and GABA level and increased MDA. Histopathologically, LCNP was significant to produce perinuclear vacuolization and hyperchromatic nuclei in the brain cortex, which indicates its damaging effects on brain. Thus, the surface modified NPs (LCNP) enhanced the penetration efficacy of LH. These studies revealed that LCNP could be effective chemical model to induce psychosis with good face, predictive and construct validity.

Protein kinase C (PRKC) isozymes activate many signaling pathways and promote tumorigenesis, which can be confirmed by masking the kinase activity. In the present study, the kinase activity of PRKC ε and ζ isozymes was masked by siRNA in bladder cancer, and the consequent gene profile was evaluated. Here, we show that the commonly dysregulated genes affected by both the isozymes were the chemokines (CXCL8 & CXCL10), adhesion molecules (ICAM1, SPP1, MMP3, VEGFA) and mutated isoform of TP53. As these same genes were upregulated in bladder cancer patients, the activity of the kinase in downregulating them is confirmed. These genes are associated with regulating the tumor microenvironment, proliferation and differentiation of cancer cells and poor prognosis. The effect of kinase masking in downregulating these genes in bladder cancer indicates the benefits PRKC inhibitors may have in managing these patients.

The present study involves the development of a reverse-phase HPLC method employing the quality-by-design methodology for the estimation of posaconazole and hemp seed oil simultaneously in nanomicelles formulation. The successful separation of posaconazole and hemp seed oil was achieved together, and this is the first study to develop and quantify posaconazole and hemp seed oil nanomicelles with linoleic acid as the internal standard and developed a dual drug analytical method employing a quality-by-design approach. The study was performed on a Shimadzu Prominence-I LC-2030C 3D Plus HPLC system with a PDA detector and the Shim-pack Solar C8 column (250 mm × 4.6 mm × 5 μm) for analysis with a mobile phase ratio of methanol:water (80:20% v/v) maintaining the flow rate of 1.0 mL/min. The final wavelength was selected as 240 nm and the elution of hemp seed oil and posaconazole was obtained at 2.7 and 4.6 min, respectively, with a maximum run time of 8.0 min. Box Behnken design was employed to optimize the method, keeping the retention time, peak area, and theoretical plates as dependent variables, while the mobile phase composition, flow rate, and wavelengths were chosen as independent variables. Parameters such as specificity, accuracy, robustness, linearity, sensitivity, precision, ruggedness, and forced degradation study were performed to validate the method. The calibration curves of posaconazole and hemp seed oil were determined to be linear throughout the range for concentration. The suggested approach can be effectively utilized for estimating the content of drugs from their nanoformulation and proved suitable for both in vivo and in vitro research.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidences reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoids, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/β-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoids also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoids against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKβ, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology-based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.