An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity.

INTRODUCTION: The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl4), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats. MATERIALS AND METHODS: Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically. RESULTS AND DISCUSSION: Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase (γ-GT) in CCl4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p<0.05 & p<0.01, respectively. On the other hand, G. procumbens and silymarin displayed Statistically significant (p<0.05) and high significant(p<0.01) increased levels of HDL, CAT SOD (here p<0.05 & p<0.01 for different doses) when the treatment groups were compared with the disease control group. Because the therapeutic activity imparted by plants and drugs accelerates the movement of the disturbed pathophysiological state toward the healthy state. In the molecular docking analysis, G. procumbens phytoconstituents performed poorly against transforming growth factor-beta 1 (TGF-ß1) compared to the control drug silymarin. In contrast, 26 phytoconstituents scored better than the control bezafibrate against peroxisome proliferator-activated receptor alpha (PPAR-α). The top scoring compounds for both macromolecules were observed to form stable complexes in the molecular dynamics simulations. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity. It can, thus, be inferred that the extract of G. procumbens showed good hepatoprotective properties in rats.

Irrational use of antibiotics and factors associated with antibiotic resistance: Findings from a cross-sectional study in Bangladesh.

Background and aims: Irrational antibiotic (AB) usage poses a serious concern to third-world countries because of poor surveillance, lack of information, and patients' propensity for self-medication. Additionally, the unpredictability of the coronavirus disease 2019 (COVID-19) pandemic promoted the abuse of ABs, which accelerated the prevalence of antibiotic resistance (ABR). The primary aim of this study was to assess the pattern of AB usage and irrational use of ABs-related potential factors associated with ABR among the students and teachers of a leading public university of Bangladesh. Methods: A cross-sectional web-based survey was conducted among the students and teachers (n = 783) of the selected university, from January 1 to February 28, 2022. Descriptive statistics, χ 2 test, and logistic regression analysis were employed to analyze the collected data. Results: The regression analysis supported that male participants had a 34% lower experience of acquiring ABR than female respondents (adjusted odds ratio [AOR] = 0.66, 95% confidence interval [CI] = 0.448, 0.973; p = 0.036). The 1st/2nd-year level students had more than two times higher experience with ABR than the master's or higher-class students (AOR = 2.149, 95% CI = 1.047, 4.412; p = 0.037). The participants who took ABs for 4-6 days showed more than two times ABR experience than those who took ABs for above 10 days (AOR = 2.016, 95% CI = 1.016, 4.003; p = 0.045). Respondents who finished their AB medication (dose completion) had a 57% less chance of acquiring ABR than the participants who did not complete their dose. Conclusion: This study found that irrational use of ABs is more prevalent among the youth and female participants. At this stage, there is an urgent need for comprehensive statutory AB control rules, as well as measures for appropriate information, education, and surveillance throughout different groups of Bangladesh.

Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application.

The pharmacological actions of benzylisoquinoline alkaloids are quite substantial, and have recently attracted much attention. One of the principle benzylisoquinoline alkaloids has been found in the unripe seed capsules of Papaver somniferum L. Although it lacks analgesic effects and is unrelated to the compounds in the morphine class, it is a peripheral vasodilator and has a direct effect on vessels. It is reported to inhibit the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) phosphodiesterase in smooth muscles, and it has been observed to increase intracellular levels of cAMP and cGMP. It induces coronary, cerebral, and pulmonary artery dilatation and helps to lower cerebral vascular resistance and enhance cerebral blood flow. Current pharmacological research has revealed that papaverine demonstrates a variety of biological activities, including activity against erectile dysfunction, postoperative vasospasms, and pulmonary vasoconstriction, as well as antiviral, cardioprotective, anti-inflammatory, anticancer, neuroprotective, and gestational actions. It was recently demonstrated that papaverine has the potential to control SARS-CoV-2 by preventing its cytopathic effect. These experiments were carried out both in vitro and in vivo and require an extensive understanding of the mechanisms of action. With its multiple mechanisms, papaverine can be considered as a natural compound that is used to develop therapeutic drugs. To validate its applications, additional research is required into its precise therapeutic mechanisms as well as its acute and chronic toxicities. Therefore, the goal of this review is to discuss the major studies and reported clinical studies looking into the pharmacological effects of papaverine and the mechanisms of action underneath these effects. Additionally, it is recommended to conduct further research via significant pharmacodynamic and pharmacokinetic studies.

Prevalence and determinants of physical violence against doctors in Bangladeshi tertiary care hospitals.

BACKGROUND: The increasing physical violence against doctors in the health sector has become an alarming global problem and a key concern for the health system in Bangladesh. This study aimed to determine the prevalence and associated factors of physical violence against doctors in Bangladeshi tertiary care hospitals. METHODS: A cross-sectional survey was performed among 406 doctors working in tertiary care hospitals. Data were collected using a self-administered questionnaire and the binary logistic regression model was employed for predicting physical violence against doctors. RESULTS: Of the participants, 50 (12.3%) doctors reported being exposed to physical violence in 12 months prior to the survey. According to logistic regression analysis, aged less than 30 years or younger, male and never-married doctors were prone to physical violence. Similarly, doctors from public hospitals and those worked in emergency departments were at higher risk of physical violence. More than 70% of victims reported that patients' relatives were the main perpetrators. Two-thirds of the victims referred to violence in the hospitals as a grave concern. CONCLUSIONS: Physical violence against doctors is relatively common in the emergency departments and public hospitals in Bangladesh. This study found that male and younger doctors were at high risk of exposing physical violence. To prevent hospital violence, authorities must develop human resources, bolster patient protocol and offer physician training.

Assessing the Self-reported After Events Following Immunization of COVID-19 Vaccines in Turkey and Bangladesh.

Though mass vaccination programs helped to reduce the severity of the ongoing pandemic, various unwanted effects were reported in Turkey and Bangladesh after taking vaccines. The purpose of this study was to evaluate and compare the adverse effects of several vaccines in Turkey and Bangladesh and how the population of both countries prioritizes the continuation of vaccination compared to the side effects. An online survey with a pretest was conducted to gather data over the research period from July 10, 2021 to December 10, 2021. Finally, the questionnaire was shared with the mass population of Turkey and Bangladesh who have received at least one or two doses of the COVID-19 vaccines. The quality of the questionnaire was evaluated with Cronbach's alpha test. The study consisted of 1508 respondents from Bangladesh and 602 respondents from Turkey. Among the total 2110 respondents, 50.0% were male 66.8% were from the 18-30 years age range, and 77.5% reported living in the city area. Among all the respondents, 64.99% of those vaccinated in Bangladesh and 67.28% of those vaccinated in Turkey reported side effects after vaccinations. Participants receiving mRNA vaccines (Pfizer and Moderna) experienced the most side effects, with many reporting pain at the injection site in both nations. Following that, fever, body pain, and headache were common in Bangladesh, whereas body pain, fatigue, and arm numbness were common in Turkey. The study found no significant adverse events reported in Turkey and Bangladesh following the first and second doses of COVID-19 vaccination. These COVID-19 vaccines showed similar patterns of efficacy and safety during the short period of analysis. Vaccines from different manufacturers showed a non-significant level of adverse events during this binational AEFI approach to COVID-19 vaccines. More studies are recommended on the efficacy and safety of several vaccines to discover unexpected effects.

A Retrospective Evaluation of Self-Reported Adverse Events Following Immunization with Different COVID-19 Vaccines in Türkiye.

BACKGROUND: The Sinovac and BioNTech vaccines were the first to be introduced in Türkiye to fight the ongoing global COVID-19 pandemic. As these vaccines had shown some side-effects in its clinical trial, we aimed to conduct a survey study to assess the short-term adverse events following immunization (AEFIs) in Türkiye. METHOD: A cross-sectional study was conducted using social and electronic media platforms by delivering a pre-formed and validated online questionnaire among people who had received at least one dose of the COVID-19 vaccine. This survey study focused on mass populations from different regions in Türkiye. A total of 603 responses were collected. Among these, 602 were selected based on complete answers and used for the assessment. The collected data were then analyzed to evaluate the various parameters related to the AEFIs of the respondents. RESULTS: Among the total 602 participants, 20.8% were male, and 78.7% were female, actively answering all of the constructive questions. Most of the respondents were between 18-30 years of age. We found that a total of 23.3% of the total respondents had been infected with the SARS-CoV-2 virus. Our survey revealed that out of 602 volunteers, the rate of experiencing physical discomfort was higher in participants who had received the Pfizer-BioNTech vaccine at all three doses than in those who had received the Sinovac vaccine. When all vaccine types were examined, the most common side effect was pain at the injection site, reported by 75.19% participants. When the side effects were compared according to vaccine types, there was a significant difference only in terms of fever. Fever rates in those who had received the Pfizer-BioNTech vaccine (20.96%) were found to be significantly higher than those who had received the Sinovac vaccine (8%). CONCLUSIONS: The studied vaccines showed minor side effects and there was no significant difference between the vaccines in terms of other side effects. Moreover, further research is needed to determine the efficacy of the existing vaccines in preventing SARS-CoV-2 infections or after-infection hospitalization.

Ethnobotanical Uses, Phytochemistry, Toxicology, and Pharmacological Properties of Euphorbia neriifolia Linn. against Infectious Diseases: A Comprehensive Review.

Medicinal plants have considerable potential as antimicrobial agents due to the presence of secondary metabolites. This comprehensive overview aims to summarize the classification, morphology, and ethnobotanical uses of Euphorbia neriifolia L. and its derived phytochemicals with the recent updates on the pharmacological properties against emerging infectious diseases, mainly focusing on bacterial, viral, fungal, and parasitic infections. The data were collected from electronic databases, including Google Scholar, PubMed, Semantic Scholar, ScienceDirect, and SpringerLink by utilizing several keywords like 'Euphorbia neriifolia', 'phytoconstituents', 'traditional uses', 'ethnopharmacological uses', 'infectious diseases', 'molecular mechanisms', 'COVID-19', 'bacterial infection', 'viral infection', etc. The results related to the antimicrobial actions of these plant extracts and their derived phytochemicals were carefully reviewed and summarized. Euphol, monohydroxy triterpene, nerifoliol, taraxerol, ß-amyrin, glut-5-(10)-en-1-one, neriifolione, and cycloartenol are the leading secondary metabolites reported in phytochemical investigations. These chemicals have been shown to possess a wide spectrum of biological functions. Different extracts of E. neriifolia exerted antimicrobial activities against various pathogens to different extents. Moreover, major phytoconstituents present in this plant, such as quercetin, rutin, friedelin, taraxerol, epitaraxerol, taraxeryl acetate, 3ß-friedelanol, 3ß-acetoxy friedelane, 3ß-simiarenol, afzelin, 24-methylene cycloarenol, ingenol triacetate, and ß-amyrin, showed significant antimicrobial activities against various pathogens that are responsible for emerging infectious diseases. This plant and the phytoconstituents, such as flavonoids, monoterpenoids, diterpenoids, triterpenoids, and alkaloids, have been found to have significant antimicrobial properties. The current evidence suggests that they might be used as leads in the development of more effective drugs to treat emerging infectious diseases, including the 2019 coronavirus disease (COVID-19).

Evaluation of Antioxidant, Cytotoxic, Anti-Inflammatory, Antiarthritic, Thrombolytic, and Anthelmintic Activity of Methanol Extract of Lepidagathis hyalina Nees Root.

Lepidagathis hyalina Nees is an ethnomedicinally potential Asian herb, locally used to treat cardiovascular diseases and coughs. The study was intended to evaluate qualitative and quantitative investigation to ensure numerous pharmacological properties of methanol extracts of L. hyalina Ness root (MELHR). MELHR manifested strong radical scavenging activity in the reducing power and DPPH (1, 1-diphenyl-2-picrylhydrazyl) assays, and phenol and flavonoid in the quantitative assays. In the study of the thrombolytic assay, MELHR showed moderate explicit percentage of clot lysis (29.39 ± 1.40%) with moderate (135.35 µg/mL) toxic properties. The in vitro anti-inflammatory activity was evaluated by the inhibition of hypotonicity-induced RBC hemolysis, whereas the plant extract exhibited a significant (pp ˂ 0.005) dose-dependent inhibition and the highest inhibition was found 55.01 ± 3.22% at 1000 µg/mL concentration. Moreover, the MELHR also showed significant (p < 0.005) dose-dependent potentiality on protein denaturation which is considered as antiarthritic activity, and the peak inhibition was found significant (71.97 ± 2.71%) at 1000 µg/mL concentration. MELHR also exhibited the dose-dependent and statistically significant anthelmintic potential on aquarium worm (Tubifex tubifex). So, the present investigation suggests that L. hyalina could be the best choice for the management of cardiovascular, inflammation, arthritis, and anthelmintic diseases. Further investigation should be necessary to determine behind the mechanism of bioactivity and therapeutic potential of this plant.

In Vivo and In Silico Assessment of Diabetes Ameliorating Potentiality and Safety Profile of Gynura procumbens Leaves.

BACKGROUND: Diabetes mellitus is one of the most notable health dilemmas. Analyzing plants for new antidiabetic remedies has become an impressive territory for life science researchers. Gynura procumbens has long been used to treat diabetes. Thus, we strived to ascertain the hypoglycemic potentiality of extract of leaves of G. procumbens by in vivo and in silico approaches. METHODS: Fresh leaves of G. procumbens were collected and shade-dried to prepare ethanolic extracts to evaluate pharmacological parameters. Diabetes was induced in rats via injecting alloxan through the intraperitoneal route at a dose of 150 mg/kg body weight. Humalyzer 3000 was used to perform a biochemical assay of collected samples from rats. Anti-hyperglycemic activity study along with overdose toxicity test was performed. The pharmacological activity of this plant was also evaluated through a molecular docking study. This in silico study investigated the binding affinity of natural ligands from G. procumbens against glycoside hydrolase enzymes. RESULTS: We detected a peak plasma concentration of G. procumbens at 3 hours 45 minutes that is roughly similar to the peak plasma concentration of metformin. Again, in OGTT and anti-hyperglycemic tests, it has been ascertained that both plant extract and metformin can exert significant (P < 0.05) and highly significant (P < 0.01) hypoglycemic activity in a dose-dependent manner. Metformin exhibited better therapeutic efficacy than that of plant extract, but it possessed null statistical significance. Also, our safety profile expressed that, similar to metformin, the plant extract can restore the disturbed pathological state in a dose-oriented approach with a wide safety margin. In silico study also validated the potentialities of natural constituents of G. procumbens. Conclusion. This study suggested that G. procumbens can be considered as potential antidiabetic plant. Robust and meticulous investigation regarding plant chemistry and pharmacology in the future may bring about a new dimension that will aid in discovering antidiabetic drugs from this plant in the diabetes management system.

An evaluation of pharmacological healing potentialities of Terminalia Arjuna against several ailments on experimental rat models with an in-silico approach.

Herbal remedies have been used in many cultures for decades to treat illnesses. These medicinal plants have been found to contain various phytochemical compounds that can help to cure mild to severe illnesses. The inadequacies of conventional medicines and their unusual side effects sparked a determined search for alternative natural therapeutic agents. Another reason for this hunt could be the availability and fewer side effects of natural products. T. arjuna is widely used in traditional medicine to alleviate various diseases like relieving pain, ameliorating diabetes, mitigating inflammation, and back-pedaling of depression. In this study, the ethanolic extract of T. arjuna possesses a promising effect on the animal model (p < 0.05/p < 0.01) as an antihyperglycemic, analgesic, anti-inflammatory, and antidepressant agent, but in a dose-dependent manner. The lower dose of T. arjuna was found to be capable of reversing the disturbed physiological state at a significant level (p < 0.05). However, a higher dose of T. arjuna exerts better therapeutic effects for those diseases. This animal study aims to evaluate the anti-diabetic, anti-depressant, and anti-inflammatory properties of T. arjuna compared to conventional marketed drugs. We will perform an in-silico study for active constituents of T. arjuna against their proposed targets and look for the molecular cascade on their claimed pharmacological properties. This study shows that different doses of T. arjuna bark extracts give similar therapeutic responses compared with established marketed drugs in managing hyperglycemia, stress-induced depression, and inflammation. Besides, our docking study reveals that flavonoids and triterpenoid active constituents of T. arjuna play an important role in its usefulness. This study, therefore, scientifically confirmed the traditional use of this medicinal plant in the management of several diseased conditions.

A Retrospective Cross-Sectional Study Assessing Self-Reported Adverse Events following Immunization (AEFI) of the COVID-19 Vaccine in Bangladesh.

BACKGROUND: The Oxford-AstraZeneca vaccine (Covishield) was the first to be introduced in Bangladesh to fight the ongoing global COVID-19 pandemic. As this vaccine had shown some side-effects in its clinical trial, we aimed to conduct a study assessing short-term adverse events following immunization (AEFIs) in Bangladesh. METHOD: A cross-sectional study was conducted on social and electronic media platforms by delivering an online questionnaire among people who had taken at least one dose of the COVID-19 vaccine. The collected data were then analysed to evaluate various parameters related to the AEFIs of the respondents. RESULTS: A total of 626 responses were collected. Of these, 623 were selected based on complete answers and used for the analysis. Most of the respondents were between 30-60 years of age, and 40.4% were female. We found that a total of 8.5% of the total respondents had been infected with the SARS-CoV-2 virus. Our survey revealed that out of 623 volunteers, 317 reported various side-effects after taking the vaccine, which is about 50.88% of the total participants. The majority of participants (37.07%, 231/623) reported swelling and pain at the injection site and fever (25.84%, 162/623); these were some of the common localized and generalized symptoms after the COVID-19 vaccine administration. CONCLUSION: The side-effects reported after receiving the Oxford-AstraZeneca vaccine (Covishield) are similar to those reported in clinical trials, demonstrating that the vaccines have a safe therapeutic window. Moreover, further research is needed to determine the efficacy of existing vaccines in preventing SARS-CoV-2 infections or after-infection hospitalization.

Classification of Indoor Human Fall Events Using Deep Learning.

Human fall identification can play a significant role in generating sensor based alarm systems, assisting physical therapists not only to reduce after fall effects but also to save human lives. Usually, elderly people suffer from various kinds of diseases and fall action is a very frequently occurring circumstance at this time for them. In this regard, this paper represents an architecture to classify fall events from others indoor natural activities of human beings. Video frame generator is applied to extract frame from video clips. Initially, a two dimensional convolutional neural network (2DCNN) model is proposed to extract features from video frames. Afterward, gated recurrent unit (GRU) network finds the temporal dependency of human movement. Binary cross-entropy loss function is calculated to update the attributes of the network like weights, learning rate to minimize the losses. Finally, sigmoid classifier is used for binary classification to detect human fall events. Experimental result shows that the proposed model obtains an accuracy of 99%, which outperforms other state-of-the-art models.

A review on chemistry, source and therapeutic potential of lambertianic acid.

Lambertianic acid (LA) is a diterpene bioactive compound mainly purified from different species of Pinus. It is an optical isomer of another natural compound daniellic acid and was firstly purified from Pinus lambertiana. LA can be synthesized in laboratory from podocarpic acid. It has been reported to have potential health benefits in attenuating obesity, allergies and different cancers including breast, liver, lung and prostate cancer. It exhibits anticancer properties through inhibiting cancer cell proliferation and survival, and inducing apoptosis, targeting major signalling components including AKT, AMPK, NFkB, COX-2, STAT3, etc. Most of the studies with LA were done using in vitro models, thus warranting future investigations with animal models to evaluate its pharmacological effects such as antidiabetic, anti-inflammatory and neuroprotective effects as well as to explore the underlying molecular mechanisms and toxicological profile. This review describes the chemistry, source, purification and therapeutic potentials of LA and it can therefore be a suitable guideline for any future study with LA.

Optimal configuration and combination of multiple lignocellulosic biomass feedstocks delivery to a biorefinery.

Biomass availability and transportation are major challenges in establishing a large-scale biorefinery. The objective of this study was to assess the delivery cost of different combinations of multiple forms of lignocellulosic feedstocks including agricultural and woody biomass. Three types of biomass i.e., wheat straw, corn stover and forest biomass were considered in different forms such as loose biomass, bales/bundles, chopped/chipped and pellets. It was found that the delivery cost of a combination of woody and agricultural biomass feedstocks is lower than that for a single type of biomass. The delivery of agricultural residues as bales and woody biomass as chips is an economically attractive option with optimal combination of 30% bales and 70% wood chips to a biorefinery of capacity 5000 dry tonnes per day. The anticipated traffic congestions resulting from biomass supply to a large facility could be significantly reduced by increasing the density of biomass.

Development of agri-pellet production cost and optimum size.

Minimum production cost and optimum plant size were determined for pellet plants using agricultural biomass residue from wheat, barley and oats. Three scenarios involving minimum, average and maximum yields of straw were considered for developing a techno-economic model. The life cycle cost of producing pellets in Western Canada was estimated. The economically optimum size of production plant for the three yield scenarios in tonne year(-1) were 70,000, 150,000 and 150,000, respectively. The corresponding costs of production per tonne are $170.89, $129.42 and $122.17, respectively. However, the cost of pellets does not change much for capacities over 70,000 tonne year(-1) for both the average and maximum yields. The optimum size is same for both average and maximum yield cases. Sensitivity analyses have showed that the total cost of pellet production is most sensitive to field cost followed by transportation cost. Currently, the cost of energy from agri-pellets is higher than that of energy from natural gas.