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Diabetic Charcot neuroarthropathy (DCN), first described in 1936, occurs in less than 1% of diabetic patients, but in those diabetic subjects with distal symmetrical polyneuropathy, the overall incidence increases to 30% and the risk is even greater in those with type 1 diabetes. Factors that precipitate DCN are trauma, ischaemia due to arterio‐venous shunting, increased osteoclastic activity and inflammation. DCN usually presents with a painless swollen foot and/or ankle which is 'hot to the touch'. These clinical findings are soon followed by characteristic magnetic resonance imaging (MRI) abnormalities and later X‐ray changes. The joints that are most typically involved in chronological order are the tarsometatarsals followed by the naviculocuniform, sub‐tarsal, talonavicular and metatarsal and tarsophalangeal. The cornerstone of therapy is prolonged (3–12 months) offloading with immobilization. Bisphosphonates may possibly accelerate recovery, whereas other unproven possible therapies include rhPTH, 1–34, calcitonin and methylprednisolone, which are not only ineffective but in some cases may also prolong the time to healing. Denosumab is potentially an efficacious, if unproven, therapy to accelerate healing. The risk of amputation is high and increases in the presence of a foot ulcer. DCN is associated with manifestations of autonomic neuropathy, including cardiac denervation, so that the risks of a cardiac event and heart failure are increased with DCN. Mortality is also increased with DCN, especially in the presence of a foot ulcer. To avoid the recurrence of DCN and especially to lower the risk of the recurrence of a foot ulcer recurrence reconstructive, surgery may be needed. [ABSTRACT FROM AUTHOR]

The editorial in Frontiers in Pharmacology discusses the commercialization and industrialization of experimental pharmacology and drug discovery in 2023. It highlights the importance of innovative therapeutic agents, natural products, and network pharmacology in drug development. The editorial also presents various studies on topics such as anticancer treatments, EGFR inhibitors, metallo-β-lactamase inhibitors, Alzheimer's disease, antivirulence properties, and the uses of β-nicotinamide mononucleotide and metformin in medication development. Overall, the editorial aims to promote the development of new medicinal substances from diverse sources and encourages research in the field. [Extracted from the article]

The editorial discusses the future of experimental pharmacology and drug discovery, highlighting advancements such as Elevidys® gene therapy for Duchenne muscular dystrophy and CRISPR-Cas9 technology for beta-Thalassemia. It also explores the potential of preventive medicine, Traditional Chinese Medicine, and drug repurposing, emphasizing the importance of personalized medicine and innovative approaches in pharmacology. The article underscores the need for collaborative efforts and integration of new technologies to address challenges in drug discovery over the next decade. [Extracted from the article]

Psoriasis is a lifelong immune-driven skin condition characterized by excessive epidermal overgrowth and inflammatory cell infiltration. Gemifloxacin is a fourth-generation fluoroquinolone with improved immunomodulatory and anti-inflammatory properties that are believed to possess an attractive role in psoriasis via suppressing the production of cytokines, chemokines, and eosinophil and neutrophil chemotaxis. The aim of this research is to investigate the ameliorative effects of prolonged topical gemifloxacin (GMF) alone and combined with clobetasol propionate (CLO) on an imiquimod (IMQ)-induced mouse model of psoriasis. Forty-eight Swiss albino mice were divided into six groups of eight. All groups except the negative controls got 62.5 mg of IMQ 5% topically for 8 days. Mice in the control group (controls) got Vaseline instead. Following the induction in the IMQ 5% group, mice in treatment groups CLO 0.05, GMF 1%, GMF 3%, and CLO + GMF obtained clobetasol propionate 0.05%, GMF 1% and 3%, and a combination of both, respectively, for an additional 8 days, rendering the experiment 16 days long. Our results revealed that gemifloxacin alleviated erythematous, thickened, and scaly psoriatic lesions and inhibited the tissue level of inflammatory cytokines, including interleukin (IL)-8, IL-17A, IL-23, tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). The anti-inflammatory effect also occurred by hindering nuclear factor-kappa B (NF-κB) signaling and reversing histopathological problems. Gemifloxacin acts effectively in mitigating psoriasis-associated lesions and restricting NF-κB-mediated inflammation, recommending gemifloxacin as a promising adjuvant candidate for additional studies on the long-term treatment of autoimmune and autoinflammatory dermatoses like psoriasis. [ABSTRACT FROM AUTHOR]

The chair of pharmacology, faculty of pharmacy of the I.M. Sechenov First MSMU formed the Moscow school of teaching pharmacology at the Institute of Pharmacy and Pharmaceutical Institute, is a prestigious scientific pharmaceutical center. The article traces the course of the founders of the national schools of pharmacology (I.M. Dogel, N.P. Kravkov and others) developed by leading scientists (V.V. Nikolaev, M.P. Nikolaev, A.N. Kudrin) who worked at the department and created new scientific schools. The authors note the continuity of scientific traditions in the activities of the department in the course of its history. The information on the search for new approaches to the training of pharmacy, results of solving of some major issues of pharmacology are cited, which were the notable contribution of faculty in the biological and medical science.

Based on our previous work, in which acute intravenous hormone infusion reduced food intake in healthy men,[11] a sample size of 16 people would have 90% power (at a significance level of 0.05) to detect a clinically significant reduction in food intake of 2.3 ± 1.3 kcal/kg. This is the first study to report on the effect of kisspeptin on appetite, food intake, glucose and insulin levels in women, and in people who are overweight or have obesity. Keywords: appetite control; experimental pharmacology; randomized trial; weight control EN appetite control experimental pharmacology randomized trial weight control 2393 2397 5 07/04/23 20230801 NES 230801 BACKGROUND Kisspeptin is recognized to have a critical role in the control of reproductive function[[1]]; however, as reproductive processes require adequate energy stores, there is increasing focus on its interaction with metabolic processes. (B) Luteinizing hormone (LH) levels were higher during kisspeptin infusion compared with vehicle infusion (**p < .01). gl Serum insulin, plasma glucose, serum luteinizing hormone (LH) and serum oestradiol were measured in the Clinical Chemistry Laboratory of Imperial College Healthcare NHS Trust. [Extracted from the article]

Objective: to investigate the antitumor effects of various forms of vitamin B12 in combination with various synergistic vitamins and evaluate the prospects for clinical applications.Material and methods. Cell lines BT-474 (breast ductal carcinoma) and A549 (lung carcinoma) were used as an in vitro cell model, and transplantable epidermoid Lewis lung carcinoma (LLC) was used as an in vivo animal tumor model. Animal studies of LLC were carried out on 25 male F1 hybrid mice (age 2.5–3 months, body weight 23–26 g). In silico research was conducted as a systematic computer analysis of 9,326 scientific sources.Results. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) confirmed the cytotoxic effect of vitamin B12 (aquacobalamin). It has been shown that vitamin B12 has weak cytotoxic properties in the concentration range of 3.125–200 μg/L (IC50>200 nM), and its hydrophobic derivative (heptamethyl cyanoquacobyric acid ester) significantly reduces the survival of tumor lines. BT-474 and A549 cells at high concentrations (100–200 µg/l, IC50~100 nM). Experimental animals with an in vivo LLС model easily tolerated a drug based on vitamin B12. Exposure to the drug up to the 21st day of LLС development was accompanied by an increasing tendency to inhibit tumor growth by 10–20% (р=0.059). The results of a systematic in silico review of the literature show that clinical data confirmed the significant antitumor effect of vitamin B12.Conclusion. The cellular model indicated the antitumor properties of vitamin B12 and its hydrophobic derivative. With subchronic intragastric administration of B12 to tumor-bearing animals, a steady tendency to inhibit the LLС growth was observed. Analysis of clinical data confirmed the feasibility of the antitumor use of vitamin B12 individually and in combination with synergistic vitamins.

Aim: This study was done to investigate the anti‐diabetic and anti‐oxidative synergism between zinc(II) and ferulic acid through complexation. Methods: Zinc sulphate was complexed with ferulic acid in a 1:2 molar ratio. The complex was characterized using Fourier‐transform infrared spectroscopy, proton NMR and high‐resolution mass spectroscopy techniques and evaluated for cellular toxicity. In silico, in vitro, cell‐based and tissue experimental models were used to test the anti‐diabetic and anti‐oxidant activities of the complex relative to its precursors. Results: A zinc(II)‐biferulate.2H2O complex was formed. The in vitro radical scavenging, anti‐lipid peroxidative and α‐glucosidase and α‐amylase inhibitory activity of the complex was 1.7–2.1 folds more potent than ferulic acid. Zn(II) complexation increased the anti‐glycation activity of ferulic acid by 1.5 folds. The complex suppressed lipid peroxidation (IC50 = 48.6 and 331 μM) and GHS depletion (IC50 = 33.9 and 33.5 μM) in both Chang liver cells and isolated rat liver tissue. Its activity was 2.3–3.3 folds more potent than ferulic acid and statistically comparable to ascorbic acid. Zn(II) complexation afforded ferulic acid improved glucose uptake activity in L‐6 myotube (EC50 = 11.7 vs. 45.7 μM) and isolated rat muscle tissue (EC50 = 501 and 1510 μM). Complexation increased muscle tissue zinc(II) uptake and hexokinase activity. Docking scores of the complex (−7.24 to −8.25 kcal/mol) and ferulic acid (−5.75 to 6.43 kcal/mol) suggest the complex had stronger interaction with protein targets related to diabetes, which may be attributed to the 2 ferulic acid moieties and Zn(II) in the complex. Moreover, muscle tissue showed increased phospho‐Akt/pan‐Akt ratio upon treatment with complex. The complex was not hepatotoxic and myotoxic at in vitro cellular level. Conclusion: Zn(II) complexation may be promising therapeutic approach for improving the glycaemic control and anti‐oxidative potential of natural phenolic acids. [ABSTRACT FROM AUTHOR]

Capsaicin acts on sensory nerves via vanilloid receptors. TRPV1 has been extensively studied with respect to functional lower urinary tract (LUT) conditions in rodents and humans. We aimed to (1) provide background information on capsaicin and TRPV1 and its mechanisms of action and basis for clinical use, (2) review the use of acute intravesical capsaicin instillation (AICI) in rodents to mimic various LUT disorders in which capsaicin sensitive C-fibers are involved and (3) discuss future innovative treatments. A comprehensive search of the major literature databases until June 2022 was conducted. Both capsaicin-sensitive and resistant unmyelinated bladder afferent C-fibers are involved in non-neurogenic overactive bladder/detrusor overactivity (OAB/DO). AICI is a suitable model to study afferent hyperactivity mimicking human OAB. Capsaicin-sensitive C-fibers are also involved in neurogenic DO (NDO) and potential targets for NDO treatment. AICI has been successfully tested for NDO treatment in humans. Capsaicin-sensitive bladder afferents are targets for NDO treatment. TRPV1-immunoreactive nerve fibers are involved in the pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS). The AICI experimental model appears relevant for the preclinical study of treatments targeting bladder afferents for refractory IC/BPS. The activity of capsaicin-sensitive bladder afferents is increased in experimental bladder outlet obstruction (BOO). The AICI model may also be relevant for bladder disorders resulting from C-fiber hyperexcitabilities related to BOO. In conclusion, there is a rationale for the selective blockade of TRPV1 channels for various bladder disorders. The AICI model is clinically relevant for the investigation of pathophysiological conditions in which bladder C-fiber afferents are overexcited and for assessing innovative treatments for bladder disorders based on their pathophysiology. [ABSTRACT FROM AUTHOR]

Background and objective: Lonicera japonica Flos (LJF) is a well-known traditional herbal medicine that has been used as an anti-inflammatory, antibacterial, antiviral, and antipyretic agent. The potent anti-inflammatory and other ethnopharmacological uses of LJF make it a potential medicine for the treatment of nonalcoholic fatty liver disease (NAFLD). This research is to explore the mechanisms involved in the activity of LJF against NAFLD using network integration and experimental pharmacology. Materials and methods: The possible targets of LJF involved in its activity against NAFLD were predicted by matching the targets of the active components in LJF with those targets involved in NAFLD. The analysis of the enrichment of GO functional annotations and KEGG pathways using Metascape, followed by constructing the network of active components–targets–pathways using Cytoscape, were carried out to predict the targets. Molecular docking studies were performed to further support the involvement of these targets in the activity of LJF against NAFLD. The shortlisted targets were confirmed via in vitro studies in an NAFLD cell model. Results: A total of 17 active components in LJF and 29 targets related to NAFLD were predicted by network pharmacology. Molecular docking studies of the main components and the key targets showed that isochlorogenic acid B can stably bind to TNF-α and CASP3. In vitro studies have shown that LJF down-regulated the TNF-α and CASP3 expression in an NAFLD cell model. Conclusions: These results provide scientific evidence for further investigations into the role of LJF in the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Participants self-administered the oral glibenclamide suspension (0.3-6 mg/day, split dose twice daily), and fasting pre-dose blood samples were taken before each dose increase every 3-4 days (see Figure S1 for trial timeline). CONCLUSION In conclusion, low-dose glibenclamide safely reduced glucagon levels in a subpopulation of patients with T2D who had fasting hyperglucagonaemia, suggesting that inappropriately increased alpha-cell K SB ATP sb activity may be a key component in the metabolic dysregulation of diabetes. Reducing hyperglucagonaemia in type 2 diabetes using low-dose glibenclamide: Results of the LEGEND-A pilot study Keywords: antidiabetic drug; clinical trial; drug mechanism; experimental pharmacology; glucagon; type 2 diabetes EN antidiabetic drug clinical trial drug mechanism experimental pharmacology glucagon type 2 diabetes 1671 1675 5 07/11/22 20220801 NES 220801 INTRODUCTION Diabetes is a multi-hormonal disorder characterized by insufficient insulin secretion and aberrant glucagon secretion, with fasting hyperglucagonaemia leading to increased hepatic glucose production,1,2 further exacerbating hyperglycaemia. [Extracted from the article]

Shangshang Yu,1,* Qi Guo,1,* Tianqian Jia,2,* Xiaofei Zhang,1 Dongyan Guo,1 Yanzhuo Jia,1 Jia Li,1 Jing Sun1 1Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 2Haojing College of Shaanxi University of Science & Technology, Shaanxi, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Sun Tel +86 029-38184958Email 3332606446@qq.comPurpose: Acute myocardial infarction (AMI) is a cardiovascular disease with a high fatality rate. In this study, we combined network pharmacology and experimental pharmacology and discovered the potential mechanism of action and the active ingredients of the lily, Tricyrtis maculata was discovered. The monomer compound with stronger activity was discovered through in vitro cell experiments.Methods: Forty known compounds were isolated from T. maculata. Using TCMSP, Swiss Target Prediction, metaTarFisher, GeneCards and OMIM databases, targets of drug compositions and AMI-related genes were obtained, and the differential expression genes between AMI and normal tissues were extracted through the GEO database. Then, through an online mapping tool, the intersection genes were obtained to predict the possible effective components of T. maculata that can be used to treat AMI. The top five targets were selected for molecular docking via the protein–protein interaction (PPI) network to verify the binding activity between key compounds and target proteins. GO and KEGG enrichment analyses of the intersection genes were carried out with the program R to further screen key genes and effective compositions. On this basis, the compound with more optimal activity was screened and validated in vitro.Results: In this study, 40 known monomer components were selected, and 1112 predicted genes, 1655 disease genes, 1425 differentially expressed genes, 1206 GO functions and 127 KEGG pathways were obtained. The results of molecular docking showed that the binding of MMP9 with drug components is stable. Through the comprehensive research of network pharmacology and experimental pharmacology, it was shown that T. maculata intervenes in the process of AMI through multicomponent, multitarget, and multichannel synergistic effects. It is speculated that the anti-AMI effect may be related to the regulation of the Akt/FoxO/BCl signaling pathway. Cellular experiments showed that nicotiflorin has satisfactory anti-inflammatory activity and endothelial protection and can reduce the release of nitric oxide (NO), an inflammatory medium after endothelial cell damage.Conclusion: This study reveals the therapeutic effect and relative mechanism of extract of T. maculata extract on AMI. Analysis revealed that nicotiflorin from T. maculata is a compound with satisfactory anti-inflammatory activity and endothelial protection, which provides a new direction and treatment basis for further experimental exploration and clinical treatment.Keywords: Tricyrtis maculata, nicotiflorin, network pharmacology, experimental pharmacology, GEO data mining

Background and Aim: Senecio rhizomatus Rusby (SrR) is a medicinal plant of the Asteraceae family and traditionally consumed as infusion in the Andean region from Peru for inflammatory disorders. This study aimed to determine the histopathological changes afforded by SrR in 7, 12-dimethylbenz[α]anthracene (DMBA)-induced breast cancer (BC) in rats. Materials and Methods: An ethanolic extract of SrR aerial parts was prepared by maceration with 96% ethanol, and the chemical components were identified by gas chromatography coupled to mass spectrometry; the antioxidant activity was determined by 1,1-diphenyl-2-picril-hidrazil (DPPH) assay; and the acute toxicity was assessed according to the OCED 423 guidelines. In a pharmacological study, 30 female Holztman rats were distributed randomly into five groups, as follows. Group I: Negative control (physiological serum, 2 mL/kg); Group II. DMBA (80 mg/Kg body weight); and Groups III, IV, and V: DMBA + ethanol extract of SrR at doses of 10, 100, and 200 mg/kg, respectively. Results: The antioxidant activity of the SrR extract against DPPH was 92.50% at 200 μg/mL. The oral administration of SrR at doses of 50, 300, 2000, and 5000 mg/kg did not show any clinical evidence of toxicity or occurrence of death. The groups that received SrR presented a lower frequency of tumors and a cumulative tumor volume compared with the DMBA group (p

Cinnamon is a wildly used traditional Chinese herbal medicine for osteoarthritis (OA) treatment, but the underlying mechanism remains ambiguous. The purpose of this study is to explore the mechanism of cinnamic aldehyde (CA), a bioactive substance extracted from Cinnamon, on synovial inflammation in OA. A total of 144 CA‐OA co‐targeted genes were identified by detect databases (PubChem, HIT, TCMSP, TTD, DrugBank and GeneCards). The results of GO enrichment analysis indicated that these co‐targeted genes have participated in many biological processes including 'inflammatory response', 'cellular response to lipopolysaccharide', 'response to drug', 'immune response', 'lipopolysaccharide‐mediated signalling pathway', etc. KEGG pathway analysis showed these co‐targeted genes were mainly enriched in 'Toll‐like receptor signalling pathway', 'TNF signalling pathway', 'NF‐kappa B signalling pathway', etc. Molecular docking demonstrated that CA could successfully bind to TLR2 and TLR4. The results of in vitro experiments showed no potential toxicity of 10, 20 and 50 μM/L CA on human OA FLS, and CA can significantly inhibit the inflammation in LPS‐induced human FLS. Further experimental mechanism evidence confirmed CA can inhibited the inflammation in LPS‐induced human OA FLS via blocking the TLR4/MyD88 signalling pathway. Our results demonstrated that CA exhibited strong anti‐inflammation effect in OA FLS through blocking the activation of TLR4/MyD88 signalling pathway, suggesting its potential as a hopeful candidate for the development of novel agents for the treatment of OA. [ABSTRACT FROM AUTHOR]

Buxue Yimu Pill (BYP) is a classic gynecological medicine in China, which is composed of Angelica sinensis (Oliv.) Diels, Leonurus japonicus Houtt, Astragalus membranaceus (Fisch.) Bunge, Colla corii asini and Citrus reticulata Blanco. It has been widely used in clinical therapy with the function of enriching Blood , nourishing Qi , and removing blood stasis. The current study was designed to determine the bioactive molecules and therapeutic mechanism of BYP against hemorrhagic anemia. Herein, GC-MS and UPLC/Q-TOF-MS/MS were employed to identify the chemical compounds from BYP. The genecards database (https: //www.genecards.org/) was used to obtain the potential target proteins related to hemorrhagic anemia. Autodock/Vina was adopted to evaluate the binding ability of protein receptors and chemical ligands. Gene ontology and KEGG pathway enrichment analysis were conducted using the ClusterProfiler. As a result, a total of 62 candidate molecules were identified and 152 targets related to hemorrhagic anemia were obtained. Furthermore, 34 active molecules and 140 targets were obtained through the virtual screening experiment. The data of molecular-target (M-T), target-pathway (T-P), and molecular-target-pathway (M-T-P) network suggested that 32 active molecules enhanced hematopoiesis and activated the immune system by regulating 57 important targets. Pharmacological experiments showed that BYP significantly increased the counts of RBC, HGB, and HCT, and significantly down-regulated the expression of EPO, IL-6, CSF3, NOS2, VEGFA, PDGFRB, and TGFB1. The results also showed that leonurine, leonuriside B, leosibiricin, ononin, rutin, astragaloside I, riligustilide and levistolide A, were the active molecules closely related to enriching Blood. In conclusion, based on molecular docking, network pharmacology and validation experiment results, the enriching blood effect of BYP on hemorrhagic anemia may be associated with hematopoiesis, anti-inflammation, and immunity enhancement. [ABSTRACT FROM AUTHOR]

Capsaicin acts on sensory nerves via vanilloid receptors. TRPV1 has been extensively studied with respect to functional lower urinary tract (LUT) conditions in rodents and humans. We aimed to (1) provide background information on capsaicin and TRPV1 and its mechanisms of action and basis for clinical use, (2) review the use of acute intravesical capsaicin instillation (AICI) in rodents to mimic various LUT disorders in which capsaicin sensitive C-fibers are involved and (3) discuss future innovative treatments. A comprehensive search of the major literature databases until June 2022 was conducted. Both capsaicin-sensitive and resistant unmyelinated bladder afferent C-fibers are involved in non-neurogenic overactive bladder/detrusor overactivity (OAB/DO). AICI is a suitable model to study afferent hyperactivity mimicking human OAB. Capsaicin-sensitive C-fibers are also involved in neurogenic DO (NDO) and potential targets for NDO treatment. AICI has been successfully tested for NDO treatment in humans. Capsaicin-sensitive bladder afferents are targets for NDO treatment. TRPV1-immunoreactive nerve fibers are involved in the pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS). The AICI experimental model appears relevant for the preclinical study of treatments targeting bladder afferents for refractory IC/BPS. The activity of capsaicin-sensitive bladder afferents is increased in experimental bladder outlet obstruction (BOO). The AICI model may also be relevant for bladder disorders resulting from C-fiber hyperexcitabilities related to BOO. In conclusion, there is a rationale for the selective blockade of TRPV1 channels for various bladder disorders. The AICI model is clinically relevant for the investigation of pathophysiological conditions in which bladder C-fiber afferents are overexcited and for assessing innovative treatments for bladder disorders based on their pathophysiology.

Cutaneous drug reactions are one of the most commonly encountered clinical presentations in dermatology clinics. But apart from the common and easily diagnosed cutaneous drug reactions, many may pose a diagnostic dilemma as they may masquerade as cutaneous manifestations of skin disease themselves like for example autoimmune blistering diseases, viral exanthems, psoriasis, collagen vascular diseases etc. or vice versa. Also, what makes it important to differentiate clinically the presence of a drug reaction from a skin disease, is the concurrent use of multiple medications by the same patient and the atypical presentation of many cutaneous drug reactions. Hence, we present a case series of 3 patients, each presenting with a cutaneous drug reaction, clinically mimicking different cutaneous skin disorders. The conclusion is that adverse drug reactions act as masqueraders clinically and sometimes histopathologically. The needless use of therapy for skin specific manifestations of drug intake can be avoided as the simple step of the culprit drug cessation can result in patient improvement and resolution of the dermatosis. It can be beneficial to have know-how of the replacement medications and the protocol of drug tapering as abrupt discontinuation might be otherwise detrimental. [ABSTRACT FROM AUTHOR]

Introduction: Computer assisted learning (CAL) is an alternative tool to animal experimentation to improve cognitive skills of undergraduate students. Methodology: It was a comparative study done with undergraduate MBBS students. Students were divided equally in two groups A(68) & B (67). CAL module was integrated with theory lectures, charts and graphs to assess the learning objectives. Every demonstration was followed by assessment in the form of objective type questions and CAL viva. Data from the assessment was analysed statistically. Results: Average score for rabbit eye experiment and frog rectus muscle preparation after CAL method was improved to 17.912 + 4.645 & 19.191 + 2.576 respectively in group A(p<0.0001) and 18.552 + 3.723 & 18.896 + 3.225 respectively in group B(p<0.0001). Overall percentage of group A was improved by 18% and group B by 15% in case of rabbit eye experiment. In group A it was improved by 13% and in group B improved by 21 % in case of Frog rectus preparation. It was observed that the students were more interested and free hand for the use of CAL models without anxiety. Conclusion: Computer assisted learning is an essential integral part in present MBBS curriculum for their active learning. [ABSTRACT FROM AUTHOR]

Background and objective: Lonicera japonica Flos (LJF) is a well-known traditional herbal medicine that has been used as an anti-inflammatory, antibacterial, antiviral, and antipyretic agent. The potent anti-inflammatory and other ethnopharmacological uses of LJF make it a potential medicine for the treatment of nonalcoholic fatty liver disease (NAFLD). This research is to explore the mechanisms involved in the activity of LJF against NAFLD using network integration and experimental pharmacology. Materials and methods: The possible targets of LJF involved in its activity against NAFLD were predicted by matching the targets of the active components in LJF with those targets involved in NAFLD. The analysis of the enrichment of GO functional annotations and KEGG pathways using Metascape, followed by constructing the network of active components–targets–pathways using Cytoscape, were carried out to predict the targets. Molecular docking studies were performed to further support the involvement of these targets in the activity of LJF against NAFLD. The shortlisted targets were confirmed via in vitro studies in an NAFLD cell model. Results: A total of 17 active components in LJF and 29 targets related to NAFLD were predicted by network pharmacology. Molecular docking studies of the main components and the key targets showed that isochlorogenic acid B can stably bind to TNF-α and CASP3. In vitro studies have shown that LJF down-regulated the TNF-α and CASP3 expression in an NAFLD cell model. Conclusions: These results provide scientific evidence for further investigations into the role of LJF in the treatment of NAFLD.

HLS shows antioxidant function by reducing inflammation, the release of pro-inflammatory cytokines, and mitochondrial autophagy regulation. APE repaired the UC-induced colon mucosa injury, reduced weight loss, attenuated DAI, colon macroscopic damage index, histological inflammation, and downregulated the levels of inflammatory markers in serum and colon tissues. Keywords: medicinal plants; natural Products; oxidative Stress; inflammatory disorders; antioxidants; experimental pharmacology; drug discovery EN medicinal plants natural Products oxidative Stress inflammatory disorders antioxidants experimental pharmacology drug discovery 1 3 3 06/28/22 20220624 NES 220624 Introduction This Research Topic focused on elucidating the role of medicinal plants and natural products in oxidative and inflammatory reactions in different pathological conditions. [Extracted from the article]

Aims: To test specific mono‐agonists to the glucagon‐like peptide‐1 receptor (GLP‐1R), glucagon receptor (GCGR) and glucose‐dependent insulinotropic peptide receptor (GIPR), individually and in combination, in a mouse model of diet‐induced non‐alcoholic steatohepatitis (NASH) and fibrosis in order to decipher the contribution of their activities and potential additive effects to improving systemic and hepatic metabolism. Materials and methods: We induced NASH by pre‐feeding C57BL/6J mice a diet rich in fat, fructose and cholesterol for 36 weeks. This was followed by 8 weeks of treatment with the receptor‐specific agonists 1‐GCG (20 μg/kg twice daily), 2‐GLP1 (3 μg/kg twice daily) or 3‐GIP (30 μg/kg twice daily), or the dual (1 + 2) or triple (1 + 2 + 3) combinations thereof. A dual GLP‐1R/GCGR agonistic peptide, 4‐dual‐GLP1/GCGR (30 μg/kg twice daily), and liraglutide (100 μg/kg twice daily) were included as references. Results: Whereas low‐dose 1‐GCG or 3‐GIP alone did not influence body weight, liver lipids and histology, their combination with 2‐GLP1 provided additional weight loss, reduction in liver triglycerides and improvement in histological disease activity score. Notably, 4‐dual‐GLP‐1R/GCGR and the triple combination of selective mono‐agonists led to a significantly stronger reduction in the histological non‐alcoholic fatty liver disease activity score compared to high‐dose liraglutide, at the same extent of body weight loss. Conclusions: GCGR and GIPR agonism provide additional, body weight‐independent improvements on top of GLP‐1R agonism in a murine model of manifest NASH with fibrosis. [ABSTRACT FROM AUTHOR]

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Aims: The potential effect of regenerating (Reg) proteins in the treatment of diabetes has been indicated in the past decade, but the clinical use of Reg proteins requires more advances in translational medicine. In the present study, we produced recombinant regenerating protein 2 (rReg2), to prove its protective effect against streptozocin (STZ)‐induced diabetes in BALB/c mice. Materials and Methods: rReg2 was administrated in STZ‐induced diabetic mice. Blood glucose, body weight, serum insulin and islet β‐cell loss were determined. However, Reg2 has also been reported to serve as an autoantigen that induces autoimmune attacks on islets and aggravates diabetic development in non‐obese diabetic mice. To address this contradiction, complete Freund's adjuvant was injected to generate a model that was hypersensitive to Reg2. In this model, islet CD8 T‐cell infiltration, serum Reg2 antibody and interleukin (IL)‐4 and IL‐10, and splenic CD4+/interferon (IFN)‐γ+ T cells were determined. Results: Direct rReg2 pretreatment preserved islet β‐cell mass against STZ and improved glycaemia, body weight and serum insulin content. The protection against cell death was further confirmed in cultured mouse islets and MIN6 cells. On the other hand, significant elevations of serum Reg2 antibody and splenic CD4+/IFN‐γ+ T cells, and decreases in serum IL‐4 and IL‐10 were detected in rReg2‐vaccinated mice, which may contribute to the accelerated diabetes. Interestingly, these mice, upon further rReg2 treatment, exhibited alleviated diabetic conditions with less islet CD8+ T‐cell infiltration. Conclusion: rReg2 treatment ameliorated STZ‐induced diabetes in normal BALB/c mice. By contrast, rReg2 vaccination exacerbated, but further rReg2 treatment alleviated, the severity of STZ‐induced diabetes. Thus, the protective effect of rReg2 is predominant over the autoantigenic β‐cell destruction, supporting the potential of rReg2 in the clinical treatment of diabetes. [ABSTRACT FROM AUTHOR]

Several studies have identified specific signalling functions for inositol polyphosphates (IPs) in different cell types and have led to the accumulation of new information regarding their cellular roles as well as new insights into their cellular production. These studies have revealed that interaction of IPs with several proteins is critical for stabilization of protein complexes and for modulation of enzymatic activity. This has not only revealed their importance in regulation of several cellular processes but it has also highlighted the possibility of new pharmacological interventions in multiple diseases, including cancer. In this review, we describe some of the intracellular roles of IPs and we discuss the pharmacological opportunities that modulation of IPs levels can provide.

Aim: To investigate the effects of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin on myocardial ketone body utilization in diabetic, obese rats with spontaneously hypertensive heart failure (SHHF), after 6 months of treatment. Materials and Methods: Myocardial ketone body utilization was measured in vivo real time using a novel ketone probe (hyperpolarized [3‐13C]acetoacetate) and magnetic resonance spectroscopy (MRS). Myocardial glucose utilization and cardiac function were also determined in vivo using hyperpolarized [1‐13C]pyruvate MRS and magnetic resonance imaging (MRI), respectively. Myocardial fatty acid uptake and liver ketogenesis were assessed via protein expression. Results: At baseline, myocardial ketone and glucose utilization were both higher in SHHF compared with control rats. Six months of empagliflozin treatment in SHHF rats was associated with less obesity, lower blood pressure, reduced blood glucose and insulin levels, and increased fasting blood β‐hydroxybutyrate levels, as expected. Contrary to the hypothesis, myocardial ketone body utilization was lower in empagliflozin‐treated SHHF rats, while glucose utilization and cardiac function were unaltered and hepatic congestion was reduced, compared with vehicle‐treated SHHF rats. Conclusions: In diabetic hypertensive heart disease, empagliflozin reduces afterload without altering myocardial function and glucose utilization in the face of falling blood glucose levels, but does not enhance myocardial ketone utilization despite increased circulating levels. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance The danshen (the root of Salvia miltiorrhiza Bge.)-shanzha (the fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (DS) herb combination is a commonly used traditional Chinese medicine with cardiovascular disease (CVD) treatment potential. Materials and methods In this study, we investigated the anti-atherosclerotic effects and mechanisms of DS by the integration of network pharmacology and polypharmacology. Eight main components were selected for target fishing by PharmMapper. Results The network pharmacological study indicated that DS may target 41 proteins and 16 pathways associated with inflammation, lipid metabolism and endothelial protection, which indicates that DS probably adjusts these processes as part of its anti-atherosclerotic activities. Furthermore, this hypothesis was verified by polypharmacology using an atherosclerotic model. Histopathological examination showed that DS inhibited pathological changes in the arteries of atherosclerotic rats and reduced the intima-media thickness (IMT). DS significantly reduced the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) and increased the high-density lipoprotein-cholesterol (HDL-C) level in the blood. DS also decreased the concentrations of interleukin (IL)-1β and IL-18, indicating anti-inflammation activity. In addition, DS increased the serum levels of nitric oxide (NO) and 6-keto-prostaglandin F 1α (6-keto-PGF 1α) and decreased the serum levels of endothelin (ET) and thromboxane B 2 (TXB 2), indicating an endothelial protective effect. Conclusions In conclusion, DS has an anti-atherosclerotic ability to lower lipid concentrations and to protect endothelial function, and it also has anti-inflammatory activity. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

In this era where the pharmaceutical companies and products are hiking in its need and production it is inevitable to document the safety and toxicity along with the indications of the same. This is where the experimental study has a vital role to play. Experimental pharmacology is the science where the drug interaction with different receptors and target sites in living organism are explained. This article reviews about the different aspects of experimental pharmacology and its uses. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the specific role of the endocannabinoid/cannabinoid type‐1 (CB1R) system in modulating mitochondrial dynamics in the metabolically active renal proximal tubular cells (RPTCs). Materials and methods: We utilized mitochondrially‐targeted GFP in live cells (wild‐type and null for the CB1R) and electron microscopy in kidney sections of RPTC‐CB1R‐/‐ mice and their littermate controls. In both in vitro and in vivo conditions, we assessed the ability of CB1R agonism or fatty acid flux to modulate mitochondrial architecture and function. Results: Direct stimulation of CB1R resulted in mitochondrial fragmentation in RPTCs. This process was mediated, at least in part, by modulating the phosphorylation levels of the canonical fission protein dynamin‐related protein 1 on both S637 and S616 residues. CB1R‐induced mitochondrial fission was associated with mitochondrial dysfunction, as documented by reduced oxygen consumption and ATP production, increased reactive oxygen species and cellular lactate levels, as well as a decline in mitochondrial biogenesis. Likewise, we documented that exposure of RPTCs to a fatty acid flux induced CB1R‐dependent mitochondrial fission, lipotoxicity and cellular dysfunction. Conclusions: CB1R plays a key role in inducing mitochondrial fragmentation in RPTCs, leading to a decline in the organelle's function and contributing to the renal tubular injury associated with lipotoxicity and other metabolic diseases. [ABSTRACT FROM AUTHOR]

Aims: In type 2 diabetes impaired insulin‐induced muscle perfusion is thought to contribute to reduced whole‐body glucose uptake. In this study, we examined the effects of iloprost, a stable prostacyclin analogue, on insulin‐induced muscle capillary recruitment and whole‐body glucose uptake. Materials and Methods: In a randomized cross‐over design, 12 type 2 diabetes patients (age, 55 [46‐69] years; BMI, 33.1 [31.0‐39] kg/m2) underwent two hyperinsulinaemic‐euglycaemic clamps, one with and one without simultaneous low‐dose iloprost infusion. Contrast‐enhanced ultrasonography of the vastus lateralis muscle was performed before and during the clamp. Muscle capillary recruitment was calculated as percentage change in microvascular blood volume (MBV) before and during the clamp. Results: Insulin infusion reduced skeletal muscle MBV by ~50% compared to the fasting state (fasting, 1.77·10−4 [1.54·10−5–2.44·10−3] arbitrary units (AU); hyperinsulinaemia, 6.69·10−5 [2.68·10−6–5.72·10−4] AU; P = 0.050). Infusion of iloprost prevented this insulin‐induced skeletal muscle capillary derecruitment, from (−49.5 [−89.5 to 55.3] %) to (8.0 [−68.8 to 306.6] %), for conditions without and with iloprost, respectively. The rate of glucose disappearance (Rd) did not change significantly during iloprost infusion (17.3 [10.0‐40.8] μmol/kg/min) compared with insulin infusion alone (17.6 [9.9‐68.7] μmol/kg/min). Conclusions: Our data suggest that acute improvement in insulin‐stimulated muscle perfusion is not an attractive therapeutic approach to bypass cellular resistance to glucose uptake in type 2 diabetes. Whether long‐term improvements in insulin‐induced muscle perfusion may prove beneficial for glucose disposal remains to be determined. [ABSTRACT FROM AUTHOR]

Aim: To determine whether non‐steroidal mineralocorticoid receptor (MR) antagonists oppose metabolic syndrome‐related end‐organ, i.e. cardiac, damage. Materials and methods: In Zucker fa/fa rats, a rat model of metabolic syndrome, we assessed the effects of the non‐steroidal MR antagonist finerenone (oral 2 mg/kg/day) on left ventricular (LV) function, haemodynamics and remodelling (using echocardiography, magnetic resonance imaging and biochemical methods). Results: Long‐term (90 days) finerenone modified neither systolic blood pressure nor heart rate, but reduced LV end‐diastolic pressure and LV end‐diastolic pressure‐volume relationship, without modifying LV end‐systolic pressure and LV end‐systolic pressure‐volume relationship. Simultaneously, long‐term finerenone reduced both LV systolic and diastolic diameters, associated with reductions in LV weight and LV collagen density, while proteinuria and renal nGAL expression were reduced. Short‐term (7 days) finerenone improved LV haemodynamics and reduced LV systolic diameter, without modifying LV diastolic diameter. Moreover, short‐term finerenone increased myocardial tissue perfusion and reduced myocardial reactive oxygen species, while plasma nitrite levels, an indicator of nitric oxide (NO) bio‐availability, were increased. Conclusions: In rats with metabolic syndrome, the non‐steroidal MR antagonist finerenone opposed metabolic syndrome‐related diastolic cardiac dysfunction and nephropathy. This involved acute effects, such as improved myocardial perfusion, reduced oxidative stress/increased NO bioavailability, as well as long‐term effects, such as modifications in the myocardial structure. [ABSTRACT FROM AUTHOR]