Assessment of the hypoglycemic and anti-hemostasis effects of Paederia foetida (L.) in controlling diabetes and thrombophilia combining in vivo and computational analysis.

Paederia foetida is valued for its folk medicinal properties. This research aimed to assess the acute toxicity, hypoglycemic and anti-hemostasis properties of the methanolic extract of P. foetida leaves (PFLE). Acute toxicity of PFLE was performed on a mice model. Hypoglycemic and anti-hemostasis properties of PFLE were investigated on normal and streptozotocin-induced mice models. Deep learning, molecular docking, density functional theory, and molecular simulation techniques were employed to understand the underlying mechanisms through in silico study. Oral administration of PFLE at a dosage of 300 µg/kg body weight (BW) showed no signs of toxicity. Treatment with PFLE (300 µg/kg/BW) for 14 days resulted in a hypoglycemic condition and a 30.47% increase in body weight. Additionally, PFLE mixed with blood exhibited a 44.6% anti-hemostasis effect. Deep learning predicted the inhibitory concentration (pIC50, nM) of Cleomiscosins against SGLT2 and FXa to be 7.478 and 6.017, respectively. Molecular docking analysis revealed strong binding interactions of Cleomiscosins with crucial residues of the target proteins, exhibiting binding energies of -8.2 kcal/mol and -7.1 kcal/mol, respectively. ADME/Tox predictions indicated favorable pharmacokinetic properties of Cleomiscosins, and DFT calculations of frontier molecular orbitals analyzed the stability and reactivity of these compounds. Molecular simulation dynamics, principal component analysis and MM-PBSA calculation demonstrated the stable, compact, and rigid nature of the protein-ligand complexes. The methanolic PFLE exhibited significant hypoglycemic and anti-hemostasis properties. Cleomiscosin may have inhibitory properties for the development of novel drugs to manage diabetes and thrombophilia in the near future.

An online observational study assessing clinical characteristics and impacts of the COVID-19 pandemic on mental health: a perspective study from Bangladesh.

Purpose: The pandemic of coronavirus disease 2019 (COVID-19) has cost numerous lives and induced tremendous mental stress among people. The purpose of this research was to determine anxiety and depression levels, clinical features, and the connections between demographic variables and depression prevalence as well as anxiety prevalence among reported COVID-19 cases in Bangladesh. Methods: For the purpose of data collection, an online cross-sectional survey was carried out from May 26 to June 27, 2020, utilizing a Google adapted preformed questionnaire. The form was shared with a short overview and justification through Facebook, Twitter, Facebook messenger, Viber, and What's App. The Google form contains five parts: a brief introduction, an approval statement, demographics, clinical and radiological data, and mental health assessment by the Generalized Anxiety Disorder 7-item (GAD-7) scale and Patient Health Questionnaire (PHQ-9). Formal ethical clearance was taken from the Institute of Biological Science (IBSc), Bangladesh. Informed consent was ensured before participation. Results: One hundred and fifty-three (153) patients with COVID-19 who had an average age of 39.43 ± 17.59 years with male predominance (72%) were included. A total of 32.7% were doing health-care related jobs, and 17.7% lost their jobs due to COVID-19. Patients had a median income of 30,000 Bangladesh taka (BDT). Of all, 12.4% of the participants showed asymptomatic features, whereas 87.6% of patients were symptomatic and presented with fever (79%), cough (58.8%), myalgia (24.2%), breathlessness (23.5%), sore throat (21.6%), fatigue (19.6%), headache (13.7%), nausea and/or vomiting (11.8%), runny nose (9.8%), chest pain (9.2%), diarrhea (8.5%), stuffy nose (3.2%), ARDS (2.6%), oral ulcer (2.6%), and conjunctivitis (1.9%). Overall, the prevalence of anxiety and depression was 63.5% and 56.6%, respectively. Among the participants, 13.2% had only anxiety, 6.3% had only depression, and 50.3% had both. Conclusion: In most cases, middle age, male, and healthy workers were patients. Fever and cough were the standard presentations. Approximately two-thirds or 66.67% of patients had anxiety and depression, one or both.

Carbofuran affects cellular autophagy and developmental senescence through the impairment of Nrf2 signalling.

Carbofuran is a broad-spectrum synthetic pesticide. Its exposure to non-target mammals affects the biological system through the induction of oxidative stress. Since oxidative stress is a major contributing factor to cellular autophagy and senescence, our present investigation determined the impacts of carbofuran-induced oxidative stress on cellular autophagy and senescence. A transmembrane protein, Spinster homolog 1 (Spns1), is involved in autophagic lysosomal metabolism. Its mutation accelerates the cellular senescence and shortens the lifespan. Using a transgenic zebrafish line, expressing fluorescent microtubules-associated protein 1 light chain 3 (EGFP-LC3) at the membrane of the autophagosome, we found that carbofuran affects autophagic lysosomal biogenesis in wild-type zebrafish and exacerbates autophagic defect in spns1-mutant zebrafish. In real-time mortality study, carbofuran has shortened the lifespan of wild-type fish. Nrf2 is a stress-responsive transcription factor that regulates the expression of antioxidant genes (such as gstp1) in the prevention of oxidative stress-mediated cellular damage. To assess the effect of carbofuran on Nrf2 signalling, we established a dual-monitoring transgenic zebrafish line, expressing gstp1 promoter-driven EGFP and mCherry-tagged Neh2 domain of Nrf2. Our results suggested that the exposure of carbofuran has down-regulated both Nrf2 and Gstp1 expressions. Overall, carbofuran affects cellular autophagy and accelerates senescence by enervating the Nrf2 signalling.

Molecular identification and biological control of Ralstonia solanacearum from wilt of papaya by natural compounds and Bacillus subtilis: An integrated experimental and computational study.

Ralstonia solanacearum is a harmful pathogen that causes severe wilt disease in several vegetables. In the present study, we identified R. solanacearum from wilt of papaya by 16S rRNA PCR amplification. Virulence ability of R. solanacearum was determined by amplification of approximately 1500 bp clear band of hrpB gene. Further, in-vitro seed germination assay showed that R. solanacearum reduced the germination rate up to 26.21%, 34% and 33.63% of cucumber, bottle guard and pumpkin seeds, respectively whereas shoot and root growth were also significantly decreased. Moreover, growth inhibition of R. solanacearum was recorded using antibacterial compound from medicinal plant and antagonistic B. subtilis. Petroleum ether root extract of Rauvolfia serpentina showed highest 22 ± 0.04 mm diameter of zone of inhibition where methanolic extract of Cymbopogon citratus and ethanolic extract of Lantana camara exhibited 20 ± 0.06 mm and 20 ± 0.01 mm zone of inhibition against R. solanacearum, respectively. In addition, bioactive compounds of B. subtilis inhibited R. solanacearum growth by generating 17 ± 0.09 mm zone of inhibition. To unveil the inhibition mechanism, we adopted chemical-protein interaction network and molecular docking approaches where we found that, rutin from C. citratus interacts with citrate (Si)-synthase and dihydrolipoyl dehydrogenase of R. solanacearum with binding affinity of -9.7 kcal/mol and -9.5 kcal/mol while quercetin from B. subtillis interacts with the essential protein F0F1 ATP synthase subunit alpha of the R. solancearum with binding affinity of -6.9 kcal/mol and inhibit the growth of R. solanacearum. Our study will give shed light on the development of eco-friendly biological control of wilt disease of papaya.

Clinical manifestations and socio-demographic status of COVID-19 patients during the second-wave of pandemic: A Bangladeshi experience.

BACKGROUND: Bangladesh is a densely populated country with a substandard healthcare system and a mediocre economic framework. Due to the enormous number of people who have been unaware until now, the development of COVID-19's second-wave infection has become a severe threat. The present investigation aimed to characterize the clinical and socio-demographic characteristics of COVID-19 in Bangladesh. METHODS: A cross-sectional analysis was carried out from all the other COVID-19 patients and confirmed by RT-PCR undergoing a specialized COVID-19 hospital. From March 1 to April 15, 2021, a total of 1326 samples were collected. Samples were only obtained from non-critical COVID-19 patients as critically ill patients required emergency intensive care medications. Then, from April 17 to May 03, 2021, SARS-CoV-2 infection and clinical assessment was performed based on interim guidelines from the WHO. The diagnosis was conducted through RT-PCR. Later, identifying the symptomatic and asymptomatic patient based on checking the Clinical Observation Form (COF). The patients filled the COF form. Finally, statistical analyses were done using the SPSS 20 statistical program. RESULTS: In this investigation, a total of 326 patients were diagnosed as COVID-19 positive. Among them, approximately 19.02% (n = 62) were asymptomatic, and 80.98% (n = 264) were symptomatic. Here, the finding shows that the occurrence of this infection was varied depending on age, sex, residence, occupation, smoking habit, comorbidities, etc. However, Males (60.12%) were more affected than females (39.88%), and, surprisingly, this pandemic infected both urban and rural residents almost equally (urban = 50.92%; rural = 49.08%). Approximately 19% of the asymptomatic and 62% of symptomatic cases had at least one comorbid disorder. Interestingly, an unexpected result was exhibited in the case of smokers, where non-smokers were more affected than smokers. The study indicates community transmission of COVID 19, where people were highly infected at their occupations (35.58%), at houses (23.93%) and by traveling (12.88%). Noteworthy, according to this report, a large number (19.33%) of individuals did not know exactly how they were contaminated with SARS-CoV-2. Patients were most commonly treated by an antibiotic 95.09%, followed in second by corticosteroid 46.01%. Anti-viral drugs, remdesivir, and oxygenation are also needed for other patients. Among those, who were being treated, approximately 69.33% were isolated at home, 27.91% were being treated at dedicated COVID-19 hospitals. Finally, 96.63% were discharged without complications, and 0.03% has died. CONCLUSION: This investigation concludes that males became more infected than females. Interestingly, both urban and rural people became nearly equally infected. It noticed community transmission of SARS-CoV-2, where people were highly infected at their workplaces. A higher rate of silent transmission indicates that more caution is needed to identify asymptomatic patients. Most of the infected people were isolated at home whereas nearly one-fourth were treated at hospitals. Clinically, antibiotics were the most widely used treatment. However, the majority of the patients were discharged without complications. The current investigation would be helpful to understand the clinical manifestations and socio-demographic situations during the second wave of the COVID-19 pandemic in Bangladesh.

SARS-CoV-2 molecular identification and clinical data analysis of associated risk factors from a COVID-19 testing laboratory of a coastal region in Bangladesh.

BACKGROUND AND AIM: Outbreak of COVID-19 seems to have exacerbated across the globe, including Bangladesh. Scientific literature on the clinical data record of COVID-19 patients in Bangladesh is inadequate. Our study analyzes the clinical data of COVID-19 positive patients based on molecular identification and risk factor correlated with three variables (age, sex, residence) and COVID-19 prevalence in the four districts of Chattogram Division (Noakhali, Feni, Lakshmipur and Chandpur) with an aim to understand the trajectory of this pandemic in Chattogram, Southern Bangladesh. METHODS: A cross-sectional study is conducted in the context of RT-PCR-based COVID-19 positive 5,589 individuals diagnosed with SARS-CoV-2 infection from the COVID-19 testing laboratory, Abdul Malek Ukil Medical College, Noakhali-3800, Bangladesh. For molecular confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), standard diagnostic protocols through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) were conducted. Different patient demographics were analyzed using SPSS version 22 for exploring the relationship of three factors - age, sex, and residence with a cumulative number of COVID-19 positive cases and prevalence of COVID-19 in four districts in Chattogram division. The data was recorded between May to July, 2020. RESULTS: Among the three parameters, the present study revealed that 20-40 cohort had the highest incidence of infection rate (51.80%, n = 2895) among the different age groups. Among the infected individuals, 56.8% (n = 3177) were male and 43.2% (n = 2412) were female, denoting males being the most susceptible to this disease. Urban residents (52.7%, n = 2948) were more vulnerable to SARS-CoV-2 infection than those residing in rural areas (47.3%, n = 2641). The prevalence of COVID-19 positive cases among the four districts was recorded highest in the Noakhali district with 36.8% (n = 2057), followed by the Feni, Lakshmipur and Chandpur districts with 25.9% (n = 1448), 20.8% (n = 1163) and 16.5% (n = 921), respectively. CONCLUSIONS: This study presents a statistical correlation of certain factors linked to Bangladesh with confirmed COVID-19 patients, which will enable health practitioners and policy makers to take proactive steps to control and mitigate disease transmission.

Investigation of mechanisms involved in seed germination enhancement, enzymatic activity and seedling growth of rice (Oryza Sativa L.) using LPDBD (Ar+Air) plasma.

The study investigates the effect of LPDBD (Low Pressure Dielectric Barrier Discharge) (Ar + Air) plasma on seed germination, seedling growth and antioxidant enzyme activity of rice. Rice seeds were treated with LPDBD (Ar + Air) plasma for 2min, 4min, 6min, 8min and 10min. Seed germination rate, seedling growth, total chlorophyll content, enzymatic activity, total soluble sugar and protein concentration were increased in plants grown from the LPDBD (Ar + Air) plasma treated seeds. It was observed that the sprouting of seeds and the growth of seedlings of rice depends on the feed gases used to generate plasma and plasma processing time. In the case of plantlets germinated from the plasma-treated seeds of rice, the H2O2 level was increased significantly both in leaves and roots for 6min, 8min and 10min treatment respectively. No significant change was observed in Nitric Oxide (NO) concentration in seed, leaf, or root of plants grown from LPDBD (Ar + Air) plasma-treated seeds. The amount of total soluble sugar and protein increased significantly in the case of 2min, 4min, 6min, 8min and 10min seed treatment. Although plants exhibited no significant increase in APX activities, but a significant increase of CAT and SOD activity in the leaf and root was found. This study reveals that LPDBD (Ar + Air) plasma is involved in the elevation of ROS species in leaf and root of rice plants which is tightly regulated by the upregulation of CAT activity that ultimately enhances the seed germination and growth of rice plantlets.

Carbofuran accelerates the cellular senescence and declines the life span of spns1 mutant zebrafish.

Carbofuran is a carbamate pesticide, widely used in agricultural practices to increase crop productivity. In mammals, carbofuran is known to cause several untoward effects, such as apoptosis in the hippocampal neuron, oxidative stress, loss of memory and chromosomal anomalies. Most of these effects are implicated with cellular senescence. Therefore, the present study aimed to determine the effect of carbofuran on cellular senescence and biological ageing. Spinster homolog 1 (Spns1) is a transmembrane transporter, regulates autolysosomal biogenesis and plays a role in cellular senescence and survival. Using senescence-associated ß-galactosidase staining, we found that carbofuran accelerates the cellular senescence in spns1 mutant zebrafish. The yolk opaqueness, a premature ageing phenotype in zebrafish embryos, was accelerated by carbofuran treatment. In the survival study, carbofuran shortened the life span of spns1 mutant zebrafish. Autophagy is the cellular lysosomal degradation, usually up-regulated in the senescent cells. To know the impact of carbofuran exposure on autophagy progress, we established a double-transgenic zebrafish line, harbouring EGFP-tagged LC3-II and mCherry-tagged Lamp1 on spns1 mutant background, whereas we found, carbofuran exposure synergistically accelerates autolysosome formation with insufficient lysosome-mediated degradation. Our data collectively suggest that carbofuran exposure synergistically accelerates the cellular senescence and affects biological ageing in spns1 defective animals.