A review on efforts for improvement in medicinally important chemical constituents inAconitum through biotechnological interventions.

The genus Aconitum belongs to the family Ranunculaceae, is endowed with more than 350 species on the earth. Medicinally important aconitine type of diterpenoid alkaloids are the characteristic compounds in most of the Aconitum species. The present review endeavored the major research carried out in the field of genetic resource characterization, pharmacological properties, phytochemistry, major factors influencing quantity, biosynthetic pathways and processing methods for recovery of active ingredients, variety improvement, propagation methods, and important metabolite production through cell/organ culture of various Aconitum species. More than 450 derivatives of aconitine-type C19 and C20-diterpenoid alkaloids along with a few other non-alkaloidal compounds, such as phenylpropanoids, flavonoids, terpenoids, and fatty acids, have been identified in the genus. A few Aconitum species and their common diterpenoid alkaloid compounds are also well characterized for analgesic, inflammatory and cytotoxic properties. However, the different isolated compound needs to be validated for supporting other traditional therapeutical uses of the plant species. Aconitine alkaloids shared common biosynthesis pathway, but their diversification mechanism remains unexplored in the genus. Furthermore, the process needs to be developed on secondary metabolite recovery, mass-scale propagation methods, and agro-technologies for maintaining the quality of products. Many species are losing their existence in nature due to over-exploitation or anthropogenic factors; thus, temporal monitoring of the population status in its habitat, and suitable management programs for ascertaining conservation needs to be developed.

Saroglitazar suppresses the hepatocellular carcinoma induced by intraperitoneal injection of diethylnitrosamine in C57BL/6 mice fed on choline deficient, l-amino acid- defined, high-fat diet.

BACKGROUND: Saroglitazar is a novel PPAR-α/γ agonist with predominant PPAR-α activity. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. In view of these observations, and the fact that NASH is a progressive disease leading to HCC, we hypothesized that saroglitazar may prevent the development of HCC in rodents. METHODS: HCC was induced in C57BL/6 mice by a single intraperitoneal injection of 25 mg/kg diethylnitrosamine (DEN) at the age of 4 weeks and then feeding the animal a choline-deficient, L-amino acid- defined, high-fat diet (CDAHFD) for the entire study duration. Eight weeks after initiation of CDAHFD, saroglitazar (1 and 3 mg/kg) treatment was started and continued for another 27 weeks. RESULTS: Saroglitazar treatment significantly reduced the liver injury markers (serum ALT and AST), reversed hepatic steatosis and decreased the levels of pro-inflammatory cytokines like TNF-α in liver. It also resulted in a marked increase in serum adiponectin and osteopontin levels. All disease control animals showed hepatic tumors, which was absent in saroglitazar (3 mg/kg)- treatment group indicating 100% prevention of hepatic tumorigenesis. This is the first study demonstrating a potent PPARα agonist causing suppression of liver tumors in rodents, perhaps due to a strong anti-NASH activity of Saroglitazar that overrides its rodent-specific peroxisome proliferation activity. CONCLUSION: The data reveals potential of saroglitazar for chemoprevention of hepatocellular carcinoma in patients with NAFLD/NASH.

Onion Peel Waste Mediated-Green Synthesis of Zinc Oxide Nanoparticles and Their Phytotoxicity on Mung Bean and Wheat Plant Growth.

Nanoparticles and nanomaterials have gained a huge amount of attention in the last decade due to their unique and remarkable properties. Metallic nanoparticles like zinc oxide nanoparticles (ZnONPs) have been used very widely as plant nutrients and in wastewater treatment. Here, ZnONPs were synthesized by using onion peel and characterized by various sophisticated instruments like Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and field emission scanning electron microscopes (FESEM). FTIR confirmed ZnONPs synthesis due to the formation of the band in the region of 400-800 cm-1, while FESEM confirmed the spherical shape of the particles whose size varies in the range of 20-80 nm. FTIR revealed several bands from 1000-1800 cm-1 which indicates the capping by the organic molecules on the ZnONPs, which came from onion peel. It also has carbonyl and hydroxyl groups, due to the organic molecules present in the Allium cepa peel waste. The average hydrodynamic size of ZnONPs was 500 nm as confirmed by DLS. The synthesized ZnONPs were then used as a plant nutrient where their effect was evaluated on the growth of Vigna radiate (mung bean) and Triticum aestivum (wheat seeds). The results revealed that the germination and seedling of mung and wheat seeds with ZnONPs were grown better than the control seed. However, seeds of mung and wheat with ZnONPs at median concentration exposure showed an enhancement in percent germination, root, and shoot length in comparison to control. Thus, the effect of ZnONPs has been proved as a nano-based nutrient source for agricultural purposes.

Polymorphic landscape of SARS-CoV-2 genomes isolated from Indian population in 2020 demonstrates rapid evolution in ORF3a, ORF8, nucleocapsid phosphoprotein and spike glycoprotein.

India, with around 15 million COVID-19 cases, recently became the second worst-hit nation by the SARS-CoV-2 pandemic. In this study, we analyzed the mutation and selection landscape of 516 unique and complete genomes of SARS-CoV-2 isolates from India in a 12-month span (from Jan to Dec 2020) to understand how the virus is evolving in this geographical region. We identified 953 genome-wide loci displaying single nucleotide polymorphism (SNP) and the Principal Component Analysis and mutation plots of the datasets indicate an increase in genetic variance with time. The 42% of the polymorphic sites display substitutions in the third nucleotide position of codons indicating that non-synonymous substitutions are more prevalent. These isolates displayed strong evidence of purifying selection in ORF1ab, spike, nucleocapsid, and membrane glycoprotein. We also find some evidence of localized positive selections ORF1ab, spike glycoprotein, and nucleocapsid. The CDSs for ORF3a, ORF8, nucleocapsid phosphoprotein, and spike glycoprotein were found to evolve at rapid rate. This study will be helpful in understanding the dynamics of rapidly evolving SARS-CoV-2.

Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis.

Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or, when not provided, indirectly estimated from each manuscript. Summary survival curves for 5-year OS and estimating survival probability by HPV status at pre-specified time intervals from study-specific Kaplan-Meier curves generated 2-year DFS. Log HRs and log CIs were combined across studies to generate summary estimates and a corresponding 95% CIs for OS and DFS. We identified ten unique studies reporting on OS and four for DFS. We observed a significant association between HPV and OS (summary HR = 0.51, 95% CI: 0.38-0.70) with relatively low heterogeneity between studies. These results indicate that HPV is a significant predictor of more favorable survival for SNSCC, and thus may be a useful biomarker for prognostication and, potentially, treatment modulation.

Lansoprazole a Proton Pump Inhibitor Prevents IBD by Reduction of Oxidative Stress and NO Levels in the Rat.

The inflammatory disease's increased prevalence leads to a major concern around the world. Still, there is a lack of effective and successful therapy in the reversal of Inflammatory Bowel Disease (IBD) symptoms. Whereas, reactive oxygen species (ROS) production and muddled defense capacity of antioxidants in IBD subjects reported several times. Many proton pump inhibitors have been reported previously for their anti-inflammatory effect. The present study is aimed to assess the ameliorative effect of lansoprazole in experimentally induced IBD in rats. Thirty-six female Sprague Dawley rats were divided equally into six groups based on their body weight. Lansoprazole (1, 5, and 10 mg/kg, p.o.) and 5-aminosalicylate (5-ASA, 100 mg/kg, p.o.) served as standard control respectively, given for 18 days once a day. On the 11th day of the study, colitis was induced by intrarectal instillation of 2, 4-Dinitrobenzene sulfonic acid (DNBS), and treatment was continued for the next 7 days. Administration of lansoprazole (at 5 and 10 mg/kg) significantly reduced DAI (Disease Activation Index) and CMDI (Colon Macroscopic Damage Index); which further justifies a reduction in colon inflammation grades, as well as histopathological changes, and reflected by the stalling of body weight. The anti-inflammatory effects were indicated by lowered MPO (myeloperoxidase) and SOD (superoxide dismutase) in colon tissue as well as restores colonic NO (nitric oxide) level. The study shows lansoprazole improved DAI and CMDI scores, reduction of neutrophil infiltration, and an improved antioxidant status indicating an anti-ulcerative effect in DNBS-induced experimental colitis that is comparable with 5-ASA treatment.

Modulation of Nrf2 by quercetin in doxorubicin-treated rats.

Doxorubicin (DOXO), a potent and widely used chemotherapeutic agent, causes irreversible heart failure by increasing oxidative stress, which limits its clinical utility. Nuclear factor erythroid-derived 2 -like 2 (Nrf2) is a prominent central regulator of cellular impenetrable to oxidants. The purpose of the study is to assess the ameliorative outcome of quercetin in cardiomyopathic rats induced by doxorubicin. Cardiomyopathy was produced in rats by single intraperitoneal weekly with DOXO (2 mg/kg) for 4 weeks. The rats were divided into five groups: (I) control group; (II) DOXO (2 mg/kg, i.p.) group; (III-V) DOXO + quercetin (10 mg/kg, 25 mg/kg and 50 mg/kg, orally), and were treated for 7 weeks. At the end of the treatment duration, cardiac function and biochemical parameters were assessed. Quercetin (10 mg/kg, 25 mg/kg and 50 mg/kg, orally) treatment reduced the raised blood pressure (BP) and left ventricular dysfunction. Withal, it prevented the rise in CKMB and LDH, suggesting the effect of quercetin in the maintaining the integrity of the cell membrane Besides, it also prevented the alteration in electrolyte levels, the activity of ATPase, and antioxidant status. Quercetin increased Nrf2 mRNA expression and reduced histological abnormalities compared to the DOXO control group. In conclusion, quercetin protected against DOXO- induced cardiomyopathy, by increasing expression of NRF2, and thereby increasing antioxidant defense and restoring biochemical and histological abnormalities.

Management of Diabetes Mellitus in Adults at the End of Life: A Review of Recent Literature and Guidelines.

Background: The prevalence of diabetes mellitus (DM) is rising with an increased risk of developing it as a person ages. Therefore, more persons will have comorbid DM throughout their health journey and are potentially prone to unpleasant symptoms associated with poor glycemic control at the end of life (EOL). We performed an in-depth literature review to examine evidence-based recommendations on DM management at the EOL. Design: A librarian-assisted systematic and gray literature search was performed in electronic clinical databases and Google™ for diabetes management articles (DMAs). National and international diabetes, palliative care, and general guideline websites were searched for clinical practice guidelines (CPGs). Inclusion criteria: adults ≥18 years with terminal illnesses, articles published between 2007 and 2017 with blood sugar target, monitoring frequency, and management recommendations for type 1 and type 2 DM. Exclusion criteria: conference poster abstracts and CPGs without published year or references. Two independent appraisers evaluated the CPGs using the "Rigour of Development" domain of the Appraisal of Guideline Research and Evaluation II (AGREE II) instrument. Results: Nine full-text DMAs were included for review from 2476 screened articles. Twenty-one CPG websites were searched. For the six included CPGs, the AGREE II "Rigour of Development" domain scores ranged from 6% to 34%. We found no high-quality evidence for DM management at the EOL. Treatment recommendations were based primarily on expert opinion (level IV evidence). Conclusions: Higher quality studies are required to inform a standardized approach to the management of DM at the EOL.

Intraoperative hemodynamics with vecuronium bromide and rocuronium for maintenance under general anesthesia.

AIMS: The present study is undertaken to compare the hemodynamic effects using vecuronium versus rocuronium for maintenance in patients undergoing general surgical procedures. SETTINGS AND DESIGN: It is a prospective, randomized, and cohort study. SUBJECTS AND METHODS: 100 patients were randomly divided into two groups. All patients were induced with 5 mg/kg of thiopentone sodium, and intubation conditions were achieved with 1.5 mg/kg of suxamethonium, using a well-lubricated cuffed endotracheal tube of appropriate size. When the patient started to breathe spontaneously, they were administered either 0.6 mg/kg of rocuronium (Group A) or 0.1 mg/kg of vecuronium (Group B). Hemodynamic parameters (heart rate and mean arterial pressure [MAP]) were monitored before administering the drug; at 1, 5, 10, 15, and 20 min after the drug and at the end of the surgery. STATISTICAL ANALYSIS USED: Data were compiled, analyzed and presented as frequency, proportions, mean, standard deviation, percentages, and t-test using SPSS (version 16). A P < 0.05 was considered as significant. RESULTS: The heart rate increased significantly at 1-min and 5-min after administration of rocuronium (83.76 ± 10.37 and 86.8 ± 9.98), unlike vecuronium. However, it gradually declined towards normal, and change in heart rate with either drug was not significant beyond 10 min. The MAP decreased significantly at 1-min after administration of rocuronium (96.68 ± 7.57) which later showed a gradual increasing trend when compared to vecuronium which had no statistically significant change at any time. CONCLUSIONS: For short surgical procedures rocuronium is a good alternative to vecuronium, as the drug is reasonably cardio stable, produces excellent intubation conditions, has a shorter duration of action, and shows minimal cumulative effect.

Postoperative Nausea and Vomiting: Palonosetron with Dexamethasone vs. Ondansetron with Dexamethasone in Laparoscopic Hysterectomies.

OBJECTIVES: Postoperative nausea and vomiting (PONV) is the most common complication seen following laparoscopic surgery. Our study sought to evaluate the efficacy of the newer drug palonosetron with that of ondansetron, in combination with dexamethasone, for PONV in patients undergoing laparoscopic hysterectomies. . METHODS: A total of 90 patients, aged between 30-50 years old, posted for elective laparoscopic hysterectomies under general anesthesia belonging to the American Society of Anesthesiologist (ASA) physical status I and II were included in the study. Patients were randomly divided into one of two groups (n=45). Before induction, patients in the first group (group I) received 0.075mg palonosetron with 8mg dexamethasone and patients in the second group (group II) received 4mg ondansetron with 8mg dexamethasone. Postoperatively, any incidences of early or delayed vomiting, requirement of rescue antiemetic, and side effects were recorded. Patient's hemodynamics were also monitored. Statistical analysis was done using Student's t-test, chi-square test, and Fisher's exact test. . RESULTS: Preoperative, intraoperative, and postoperative heart rate, mean arterial pressure, peripheral capillary oxygen saturation were statistically not significant (p>0.050) in either group. In group II, eight patients had nausea in the first two hours and three patients had nausea in the two to six-hour postoperative period. In group I, three patients experienced nausea in the first six hours period. Eight patients in group II had vomited in the first two-hour period compared to one patient in group I (p=0.013). The requirement of rescue antiemetic was greater in group II than group I (20% vs. 4%). No side effects of antiemetic use were observed in either group. . CONCLUSION: The combination of palonosetron with dexamethasone is more effective in treating early, delayed, and long term PONV compared to ondansetron with dexamethasone in patients undergoing elective laparoscopic hysterectomies under general anesthesia.

A comprehensive compositional analysis of heparin/heparan sulfate-derived disaccharides from human serum.

The analysis of heparan sulfate glycosaminoglycans (HSGAGs) variations in human serum at the disaccharide level has a great potential for disease diagnosis and prognosis. However, the lack of available analytical methodology for the compositional analysis of HSGAGs in human serum remains to be addressed to delineate the possible role of HSGAGs on the onset and/or progression of a disease. In this study, we have developed a method for the in-depth compositional analysis of the 12 heparin/HS-derived disaccharides from human serum using a combination of technologies--fractionation, exhaustive digestion, solid phase extraction, and LC-MS/MS. The method exhibits high recovery (72-110%) and good reproducibility (standard deviation of less than 5%) with a low limit of detection and quantification. Errors from the method validation were within 1.1%. Nondetectable non- or low-sulfated disaccharides in human serum were also detected using the optimized protocol. Further applying this method, the comprehensive analysis of HSGAGs compositions in human sera from female donors showed considerable variations in disaccharide patterns and compositions.

Validity of self-reported comorbidities in systemic sclerosis.

OBJECTIVE: To assess the validity of self-reports by patients with systemic sclerosis (SSc) of 5 common, chronic conditions (hypertension, diabetes, cancer, depression, and osteoarthritis/back pain) as compared to chart review. METHODS: SSc patients at a large referral hospital self-reported on a number of comorbidities. Their inpatient and outpatient medical records were abstracted using a standardized data extraction form. Sensitivity, specificity, and positive predictive value of the self-reported diagnoses were calculated using data from the chart review as gold standard. RESULTS: Self-reported comorbidity data were verified by chart review for 130 patients with SSc. The sensitivity of the self-reports for the 5 comorbid conditions was low [range 35% (cancer) to 86% (diabetes)]. The specificity was moderate to high [range 76% (osteoarthritis/back pain) to 99% (cancer)]. The positive predictive values ranged from 31% (depression) to 86% (cancer). CONCLUSION: Self-reports of comorbidities do not provide optimal data for the identification of common, chronic conditions in patients with SSc.