Physiological and transcriptomic study reveal SeNPs-mediated AsIII stress detoxification mechanisms involved modulation of antioxidants, metal transporters, and transcription factors in Glycine max L. (Merr.) roots.

Physiological changes and genome-wide alteration in gene expression were performed in soybean (Glycine max [L.] Merr.) roots exposed to AsⅢ (25 µmol/L) alone and supplemented with selenium nanoparticles (SeNPs) at the concentration of 10 and 25 µmol/L at the V2 growth stage. Excessive arsenic in the root zone poses a potential threat to soybean yield, particularly to roots, due to the limited translocation of AsIII from root to shoot in the case of soybean. We hypothesized that SeNPs can relieve AsⅢ toxicity to soybean root by reducing the AsⅢ uptake and regulating the internal tolerance mechanism of the plants. Results accomplished that SeNPs had positive impact on soybean dry weight and roots parameters under AsⅢ stress. Then, we further evaluated physiological indexes, whole genome transcriptomic analysis and quantitative real-time PCR to elucidate the underlying mechanism of AsⅢ tolerance under SeNPs supplementation. Under the condition of AsⅢ-stress, SeNPs exposure significantly reduced the electrolyte leakage, O2-•, H2O2 and MDA accumulation while increasing the antioxidants level. The RNA-seq dataset revealed total of 5819 up and 7231 down expressed DEGs across all libraries. The number of exclusively regulated genes were higher under As + SeNP10 (4909) treatment than in the AsⅢ-alone (4830) and As + SeNP25 (3311) treatments. The KEGG and GO analyses revealed that stress responsive DEGs such as glutathione S-transferase, glutathione peroxidase, ascorbate, glutaredoxin, thioredoxin, and phytochelatins synthase are responsible for AsⅢ tolerance under the SeNPs supplementation. Similarly, sulfate transporter, and ABC transporters (ATP-binding cassettes) expression were induced, and aquaporin channels related DEGs expression were reduced under SeNPs application in AsⅢ exposure condition. Furthermore, the expression of molecular chaperones (HSP) and transcription factors (MYB, bZIP, bHLH, and HSFs) were increased in SeNPs treatment groups. These results provide vital information of AsⅢ tolerance mechanism in response to SeNPs in soybean. We suggest that functional characterization of these genes will help us learn more about the SeNPs responsive arsenic tolerance mechanism in soybean.

Plant Microbiome Engineering: Hopes or Hypes.

Rhizosphere microbiome is a dynamic and complex zone of microbial communities. This complex plant-associated microbial community, usually regarded as the plant's second genome, plays a crucial role in plant health. It is unquestioned that plant microbiome collectively contributes to plant growth and fitness. It also provides a safeguard from plant pathogens, and induces tolerance in the host against abiotic stressors. The revolution in omics, gene-editing and sequencing tools have somehow led to unravel the compositions and latent interactions between plants and microbes. Similarly, besides standard practices, many biotechnological, (bio)chemical and ecological methods have also been proposed. Such platforms have been solely dedicated to engineer the complex microbiome by untangling the potential barriers, and to achieve better agriculture output. Yet, several limitations, for example, the biological obstacles, abiotic constraints and molecular tools that capably impact plant microbiome engineering and functionality, remained unaddressed problems. In this review, we provide a holistic overview of plant microbiome composition, complexities, and major challenges in plant microbiome engineering. Then, we unearthed all inevitable abiotic factors that serve as bottlenecks by discouraging plant microbiome engineering and functionality. Lastly, by exploring the inherent role of micro/macrofauna, we propose economic and eco-friendly strategies that could be harnessed sustainably and biotechnologically for resilient plant microbiome engineering.

Mahanimbine isolated from Murraya koenigii inhibits P-glycoprotein involved in lung cancer chemoresistance.

P-glycoprotein (P-gp), a transmembrane glycoprotein, is mainly involved in lung cancer multidrug resistance. Several P-gp inhibitors have been developed to enhance the efficacy of chemotherapeutics and overcome drug resistance. However, most of them failed in the clinical stages due to undesirable side effects. Therefore, there is a requirement to develop P-gp inhibitors from natural sources. Dietary spice bioactives have been well-known for their anticancer activities. However, their role in modulating the P-gp activity has not been well investigated. Therefore, we have screened for the potential bioactives from various spice plants with P-gp modulatory activity using computational molecular docking analysis. The computational analysis revealed several key bioactives from curry leaves, specifically mahanimbine, exhibited a strong binding affinity with P-gp. Unfortunately, mahanimbine is available with few commercial sources at very high prices. Therefore, we prepared a curry leaves extract and isolated mahanimbine by a novel, yet simple, extraction method that requires less time and causes minimum environmental hazards. After purification, structure, and mass were confirmed for the isolated compound by IR spectrum and LC-MS/MS analysis, respectively. In the mechanistic study, hydrolysis of ATP and substrate efflux by P-gp are coupled. Hence, ATP binding at the ATPase-binding site is one of the fundamental steps for the P-gp efflux cycle. We found that mahanimbine demonstrated to stimulate P-gp ATPase activity. Concurrently, it enhanced the intracellular accumulation of P-gp substrates Rhodamine 123 and Hoechst stain, which indicates that mahanimbine modulates the function of P-gp. In addition, we have analyzed the complementary effect of mahanimbine with the chemotherapeutic drug gefitinib. We found that mahanimbine synergistically enhanced gefitinib efficiency by increasing its intracellular accumulation in lung cancer cells. Overall, mahanimbine has been shown to be a potent P-gp modulator. Therefore, mahanimbine can be further developed as a potential candidate to overcome chemoresistance in lung cancer.

Antiviral drug research for Japanese encephalitis: an updated review.

Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and sub-urban regions of Asian countries. Although only 1% of JEV-infected individuals develop JE, there is a 20-30% chance of death among these individuals and possible neurological sequelae post-infection. No licensed anti-JE drugs are currently available, despite extensive efforts to develop them. Literature search was performed using databases such as PubMed Central, Google Scholar, Wiley Online Library, etc. using keywords such as Japanese encephalitis virus, antiviral drugs, antiviral drug screening, antiviral drug targets, etc. From around 230 papers/abstracts and research reviews retrieved and reviewed for this study, approximately 180 most relevant and important ones have been cited. Different approaches in drug testing and various antiviral drug targets explored so far have been thoroughly searched from the literature and compiled, besides addressing the future perspectives of the antiviral drug development strategies. Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent advancements in understanding the biology of infection and new drug targets have been promising improvements. Despite hindrances such as the unavailability of a proper drug delivery system or a treatment regimen irrespective of the stage of infection, several promising anti-JE candidate molecules are in different phases of clinical trials. Nonetheless, efficient therapy against JEV is expected to be achieved with drug combinations and a highly targeted drug delivery system soon.

Effect of post-diagnosis exercise on depression symptoms, physical functioning and mortality in breast cancer survivors: A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Cancer is the second leading cause of death worldwide. Breast cancer, the most common cancer found in women, affects 2.1 million women annually and has the highest number of cancer related deaths. The objective of the current meta-analysis is to evaluate the effects of post-diagnosis exercises on depression, physical functioning, and mortality in breast cancer survivors. METHODS: The search for eligible articles was conducted through CINAHL, Medline/PubMed, Scopus, Cochrane, Emerald Insight and Web of Science, Embase database, MEDLINE In-Process, Elsevier, Google Scholar, PsycInfo, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Allied and Complementary Medicine (AMED), Biosis Previews, SPORTDiscus, PEDro scientific databases from 1974 to 2020. Following the exclusion procedure, 26 articles yielded for final analysis. The combined statistics for depression, physical functioning, and mortality in breast cancer survivors were calculated using standardized mean differences (SMD). Standard errors and 95% confidence intervals (CI) were converted to standard deviations as required. For mortality, combined statistics were calculated using hazard ratios (HR). The 95% CIs were converted to standard errors as required. The forest plots display point estimates and 95% CIs. RESULTS: Statistically significant improvements on levels of depression were identified following the exercise intervention, suggesting that post-diagnosis physical activity leads to a decrease in depression scores. Overall, post-diagnosis exercise led to a 37% reduction in the rate of breast cancer-specific mortality. The all-cause mortality rate was decreased by 39% with the inclusion of moderate physical activity as the part of daily routine. CONCLUSIONS: Future studies should look at how to improve the quality of life while incorporating physical activity as a daily routine after breast-cancer treatment.

Traditional medicinal plants against replication, maturation and transmission targets of SARS-CoV-2: computational investigation.

COVID-19 is an infectious pandemic caused by the SARS-CoV-2 virus. The critical components of SARS-CoV-2 are the spike protein (S-protein) and the main protease (Mpro). Mpro is required for the maturation of the various polyproteins involved in replication and transcription. S-protein helps the SARS-CoV-2 to enter the host cells through the angiotensin-converting enzyme 2 (ACE2). Since ACE2 is required for the binding of SARS-CoV-2 on the host cells, ACE2 inhibitors and blockers have got wider attention, in addition to S-protein and Mpro modulators as potential therapeutics for COVID-19. So far, no specific drugs have shown promising therapeutic potential against COVID-19. The current study was undertaken to evaluate the therapeutic potential of traditional medicinal plants against COVID-19. The bioactives from the medicinal plants, along with standard drugs, were screened for their binding against S-protein, Mpro and ACE2 targets using molecular docking followed by molecular dynamics. Based on the higher binding affinity compared with standard drugs, bioactives were selected and further analyzed for their pharmacological properties such as drug-likeness, ADME/T-test, biological activities using in silico tools. The binding energies of several bioactives analyzed with target proteins were relatively comparable and even better than the standard drugs. Based on Lipinski factors and lower binding energies, seven bioactives were further analyzed for their pharmacological and biological characteristics. The selected bioactives were found to have lower toxicity with a higher GI absorption rate and potent anti-inflammatory and anti-viral activities against targets of COVID-19. Therefore, the bioactives from these medicinal plants can be further developed as phytopharmaceuticals for the effective treatment of COVID-19.Communicated by Ramaswamy H. Sarma.

Instrument assisted soft tissue mobilization- an emerging trend for soft tissue dysfunction.

Musculoskeletal disorders are common conditions involving joints, muscles, nerves, ligaments and tendons. These disorders affect normal activities and cause discomfort. These discomforts are managed by different types of interventions, including exercise, acupuncture, soft tissue release and manual therapy, as conservative modes of management. Soft tissue release, including active release technique, fascial abrasion, and myo-fascial release are considered effective for musculoskeletal function improvement. Advanced technology-improved and instrument-assisted techniques are being used nowadays. These instruments are sensitive in the localisation, specification and facilitation of the target area with the help of mechanical pressure applied on tissue with movement of specific muscle. Prognosis varies with good outcomes using fewer sessions than the others. But it needs proper localisation of the muscle involved and special training. The advantage considered is that musculoskeletal disorders can also be prevented in practitioners as well.

Promising phytochemicals of traditional Himalayan medicinal plants against putative replication and transmission targets of SARS-CoV-2 by computational investigation.

BACKGROUND: Identification and repurposing of therapeutic and preventive strategies against COVID-19 are rapidly undergoing. Several medicinal plants from the Himalayan region have been traditionally used to treat various human disorders. Thus, in our current study, we intended to explore the potential ability of Himalayan medicinal plant (HMP) bioactives against COVID-19 using computational investigations. METHODS: Molecular docking was performed against six crucial targets involved in the replication and transmission of SARS-CoV-2. About forty-two HMP bioactives were analyzed against these targets for their binding energy, molecular interactions, inhibition constant, and biological pathway enrichment analysis. Pharmacological properties and potential biological functions of HMP bioactives were predicted using the ADMETlab and PASS webserver respectively. RESULTS: Our current investigation has demonstrated that the bioactives of HMPs potentially act against COVID-19. Docking results showed that several HMP bioactives had a superior binding affinity with SARS-CoV-2 essential targets like 3CLpro, PLpro, RdRp, helicase, spike protein, and human ACE2. Based on the binding energies, several bioactives were selected and analyzed for pathway enrichment studies. We have found that selected HMP bioactives may have a role in regulating immune and apoptotic pathways. Furthermore, these selected HMP bioactives have shown lower toxicity with pleiotropic biological activities, including anti-viral activities in predicting activity spectra for substances. CONCLUSIONS: Current study results can explore the possibility of HMPs as therapeutic agents against COVID-19.

Heavy Metals Level, Health Risk Assessment Associated with Contamination of Black Tea; A Case Study from Khyber Pakhtunkhwa (KPK), Pakistan.

In the present study, 15 different commercial tea brands sold in Khyber Pakhtunkhwa were collected from the markets. The samples were analyzed for the concentrations of ten selected heavy metals. The metal concentration showed a random distribution in all samples. The mean concentration of Cd, Cu, Mn, Pb, Zn, and Fe was found in the range of 0.029-0.094 mg kg-1, 7.11-12.30 mg kg-1, 20.73-24.17 mg kg-1, 0.159-0.824 mg kg-1, 1.136-2.938 mg kg-1, and 0.670-118.30 mg kg-1 respectively. Co, Cr, Ni, and Sb were found below the detection limit of the instrument. Cu and Mn were found to be the abundant metals with a high concentration in the collected samples. The estimated daily intake (EDI), target hazard quotients (THQs), and hazard index (HI) were used for the assessment of health risks associated with the intake of metals. The metal transfer rates to tea infusion were reported from previous studies. Except for Cu, the EDI values of all the elements were found to be lower than the RfD values. The corresponding HI values of metals, in the different tea brands, were found to be below 1 suggesting that the consumption of mature tea infusions in the studied area could cause no carcinogenic risk. The principle cluster analysis (PCA) was used to reduce the number of variables to a new set which extracted three factors. For the assessment of health risks associated with dietary metal exposure, constant determination of heavy metals in all food is necessary. The present study provides valuable information to the general public about the consumption of tea infusions.

Use of complementary and alternative medicine in pediatric chronic viral hepatitis.

OBJECTIVE: The objectives of the present study were to assess the prevalence, frequency and type of complementary and alternative medicine (CAM) used by children with chronic viral hepatitis infection, and to determine correlates of use and estimates of nondisclosure regarding CAM use. PATIENTS AND METHODS: In this cross-sectional pilot study, families of 68 children receiving care for chronic viral hepatitis at a tertiary medical center were administered a survey regarding use of CAM. RESULTS: Forty-six percent of these families reported using CAM for their child at least once since diagnosis with chronic viral hepatitis and 31% used CAM monthly or more frequently. Of all of the CAM therapies, biologically based products such as herbals and dietary supplements were used most often. Use of CAM was independently associated with the current or previous use of antiviral medications for viral hepatitis, parent's use of CAM, and child having a nonliver comorbidity. Rates of physician nondisclosure regarding CAM use were >60%. CONCLUSIONS: This is the first report of CAM use in children with chronic viral hepatitis. Use of CAM in this population is common, and despite published adult reports, there is infrequent dialogue between patients and pediatric health care providers regarding use of CAM.

Factors predicting hyperkalemia in patients with cirrhosis receiving spironolactone.

OBJECTIVE: To evaluate the factors leading to hyperkalemia in patients with cirrhosis receiving spironolactone. DESIGN: An observational, analytical, case control study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital. Six months. SUBJECTS AND METHODS: One hundred and fifty consecutive patients (100 males, 50 females) with cirrhosis of liver, hospitalized for decompensated disease and receiving spironolactone for at least two weeks before admission, were included in this study. Patients with hyperkalemia (n=67) having potassium level >5 mmol/l were compared with patients who had normal potassium level 5 mmol/l (n=83). The parameters taken into account were age, gender of the patients, type and dose of diuretics along with concomitant medicines, diastolic blood pressure, edema, ascites, blood urea nitrogen, serum creatinine, electrolytes, bilirubin, albumin, prothrombin time, Child class, and Child Pugh score. RESULTS: Patients with hyperkalemia (K > 5 mmol/l) had higher blood urea nitrogen, serum creatinine and bilirubin levels (p= 0.004, 0.001 and 0.044 respectively). Their serum sodium and albumin levels were lower (p= 0.000 and 0.017 respectively). They had advanced cirrhosis with high Pugh score (p= 0.003). These patients were on higher dose of spironolactone (p =0.001). Multivariate analysis showed that dose of spironolactone >100 mg /day, serum creatinine >1.3 mg/dl, persistence of ascites and edema, and female gender were important predictors of development of hyperkalemia. CONCLUSION: Patients with cirrhosis receiving high dose of the diuretic, having edema, ascites and high serum creatinine are at the greater risk of developing hyperkalemia during spironolactone therapy.