Search

Cucumis melo var. agrestis (Naudin) is an important wild crop that belongs to the family Cucurbitaceae. Fruits possess digestive, stomachic, vermifuge and febrifuge properties and possess analgesic, antioxidant, antibacterial and anti-inflammatory activities. Current research is aimed at screening diverse phytoconstituents present in the fruit extract of wild melon ( C. melo var. agrestis ) with the technique of high-performance liquid chromatography (HPLC). Our outcomes showed that fruit extract of C. melo var. agrestis has various phytochemicals such as glycosides, alkaloids, phenols, flavonoids, saponins, tannins, proteins, amino acids and carbohydrates. HPLC analysis revealed that naringenin and catechin were reported to have the highest concentrations among the all studied accessions. PCA and HCA multivariant analysis showed that, first two principal components, i.e. PC1 and PC2 contributed to 54.87% of the variation, where maximum loadings were from apigenin, trailed by gallic acid, rutin, and catechol.

Background: Availability of antibiotics without prescription contributes to the rising threat of antibiotic resistance due to widespread self-medication and improper use. In this study, we aimed to assess the antibiotic market in Bangladesh according to the WHO AWaRe (Access, Watch, Reserve) classification system to better understand how the unregulated access of antibiotics may influence self-medication practices and the emergence of antibiotic resistance in the country., Methods: Data on AWaRe class antibiotics, their strengths, and dosage forms were collected from Bangladeshi drug indexing smartphone applications, the Bangladesh National Formulary (BDNF), and the Directorate General of Drug Administration (DGDA) website. Sales data were analyzed using IQVIA data to determine the market value and compound annual growth rates (CAGR) of antibiotics. The analysis focused on categorizing antibiotics according to the WHO AWaRe classification and examining their availability in various dosage forms and strengths including child-appropriate formulations., Results: Of the 81 antibiotics available in Bangladesh, 54.32 % belong to the Watch class, 30.86 % to Access, 8.64 % to Reserve, and 6.17 % were unclassified. In terms of ATC classifcation, the majority (91.35 %) belonged to the J01 class. Most antibiotics were available in multiple dosage forms and strengths, with tablets (54.87 %), injections (48.78 %), and capsules (30.48 %) being the most common. Additionally, 35.8 % of antibiotics were available as child-appropriate formulations. Oral formulations were prevalent, with 88.0 % of Access, 75.0 % of Watch, and 28.57 % of Reserve class antibiotics were available in oral dosage forms. A total of 56 antibiotic combinations were identified, including six WHO-recommended and two WHO-not-recommneded fixed-dose combinations. Watch class antibiotics dominated the market in terms of sales value and CAGR., Conclusion: The widespread availability of Watch class antibiotics, particularly in oral and child-appropriate formulations suggest a need for stricter regulation and public health interventions to curb self-medication, inappropriate marketing and use of antibiotics to mitigate the risks of resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Calotropis gigantea essential oil is utilized in outmoded medicine, therapeutics, and the cosmetic industries. However, the extreme volatility, oxidation susceptibility, and instability of this oil restricts its application. Thus, encapsulation is a more effective method of shielding this oil from unfavorable circumstances. The creation of oil/water (O/W) nanoemulsions based on Calotropis gigantea essential oil (CEO), known as CNE ( Calotropis gigantea essential oil nanoemulsions), and an assessment of its biological potential were the goals of this work. UV, fluorescence, and FT-IR methods were used for physiological characterization. Biological activities, including anti-inflammatory, anti-diabetic, and anti-cancer effects. Studies on the pharmacokinetics of CNE were conducted. CNEs encapsulation efficiency was found to be 92%. The CNE nanoemulsions had a spherical shape with polydispersity index of 0.531, size of 200 nm, and a zeta potential of -35.9 mV. Even after being stored at various temperatures for 50 days, CNE nanoemulsions remained stable. Numerous tests were used to determine the antioxidant capacity of CNE, and the following IC50 values (µl/mL) were found: iron chelating assay: 18, hydroxyl radical scavenging: 37, and nitric oxide radical scavenging activity: 58. The percentage of HeLa cells that remained viable after being treated with CNE was 41% at a higher dose of 1 µl. CNE inhibited α-amylase in a dose-dependent manner, with 72% inhibition at its higher dose of 250 µL. Research on the kinetics of drugs showed that nanoemulsions showed Higuchi pattern. This research showed potential use of Calotropis gigantea oil-based nanoemulsions in the food, cosmetic, and pharmaceutical industries.

Background: Breast cancer has the highest mortality rate among all cancers affecting females worldwide. Several new effective therapeutic strategies are being developed to minimize the number of breast cancer-related deaths and improve the quality of life of breast cancer patients. However, resistance to conventional therapies in breast cancer patients remains a challenge which could be due to several reasons, including changes in the tumor microenvironment. Attention is being diverted towards minimizing the resistance, toxicity, and improving the affordability of therapeutics for better breast cancer management. This includes personalized medicine, target-specific drug delivery systems, combinational therapies and artificial intelligence based screening and disease prediction. Nowadays, researchers and clinicians are also exploring the use of combinatorial immunotherapies in breast cancer patients, which have shown encouraging results in terms of improved survival outcomes. This study attempts to analyze the role of combinational immunotherapies in breast cancer patients, and offer insights into their effectiveness in breast cancer management., Methodology: We conducted a systematic review and meta-analysis for which we selected the randomized clinical trials (RCTs) focused on completed Phase I/II/III/IV clinical trials investigating combination immunotherapies for breast cancer. The analysis aimed to assess the efficacy of combination therapies in comparison to mono-therapies, focusing on overall survival (OS), and progression-free survival (PFS)., Results: We observed that, combination immunotherapies significantly (P<0.05) improved OS as compared to single-drug therapies in the Phase I with overall Risk ratio (RR) of 16.17 (CI 2.23,117.50), Phase II with an overall RR of 19.19 (CI 11.76,31.30) and for phase III overall RR 22.27 (CI 13.60,36.37). In the case of PFS, it was significant with RR: 12.35 (CI 2.14, 71.26) in Phase I RR 6.10 (CI 4.31, 8.64) in phase II, RR 8.95 (CI 6.09, 13.16) in phase III and RR 14.82 (CI 6.49, 33.82) in Phase IV of clinical trials., Conclusion: The observed improvements in overall survival and progression-free survival suggest that combination immunotherapies could serve as a better approach to breast cancer management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sisodiya, Kasherwal, Rani, Mishra, Kumar, Khan, Aftab, Shagufta, Singh, Gupta, Tanwar and Hussain.)

Biologically produced silver nanoparticles are becoming a more appealing option than chemically produced antioxidants and antimicrobial agents, because they are safer, easier to manufacture and have medicinal properties at lower concentrations. In this work, we employed the aqueous pomegranate peel extract (PPE) to synthesize silver nanoparticles (PPE-AgNPs), as peel extract is a rich source of phytochemicals which functions as reducing agent for the synthesis of PPE-AgNPs. Additionally, the PPE was examined quantitatively for total phenolics and total flavonoids content. PPE-AgNPs were characterized using analytical techniques including UV-Vis spectroscopy, DLS, FTIR, XRD, HRTEM and FESEM, evaluated in vitro against the plant pathogenic microbes and also for antioxidant activities. Analytical techniques (HRTEM and FESEM) confirmed the spherical shape and XRD technique revealed the crystalline nature of synthesized PPE-AgNPs. Quantitative analysis revealed the presence of total phenolics (269.93 ± 1.01 mg GAE/g) and total flavonoids (119.70 ± 0.83 mg CE/g). Biosynthesized PPE-AgNPs exhibited significant antibacterial activity against Klebsiella aerogenes and Xanthomonas axonopodis, antifungal activity against Colletotrichum graminicola and Colletotrichum gloesporioides at 50 µg/mL concentration. The antioxidant potential of biosynthesized PPE-AgNPs was analysed via ABTS (IC 50 4.25 µg/mL), DPPH (IC 50 5.22 µg/mL), total antioxidant (86.68 g AAE/mL at 10 µg/mL) and FRAP (1.93 mM Fe(II)/mL at 10 µg/mL) assays. Cytotoxicity of PPE-AgNPs was valuated using MTT assay and cell viability of 83.32% was determined at 100 µg/mL concentration. These investigations suggest that synthesized PPE-AgNPs might prove useful for agricultural and medicinal purposes in the future., (© 2024. The Author(s).)

In the present research, ten species of Asparagus from North India have been analysed for secondary metabolites. The quantitative study of shatavarin IV, sarsasapogenin, caffeic acid, β-sitosterol, and lupeol in the cladodes and roots of Asparagus was conducted using a validated HPTLC method. The content of sarsasapogenin was found highest in the cladodes of A. racemosus (11.20 ± 0.025 mg/g DW) and roots of A. officinalis (5.95 ± 0.024 mg/g DW). Shatavarin IV was found highest in cladodes of A. densiflorus (6.72 ± 0.02 mg/g DW) and roots of A. adscendens (4.68 ± 0.015 mg/g DW). Caffeic acid was found most abundantly in A. officinalis (65.87 ± 0.021 mg/g DW), while β-sitosterol (9.36 ± 0.004 mg/g DW) and lupeol (5.91 ± 0.004 mg/g DW) were found highest in A. falcatus among the ten species. Overall findings showed that A. adscendens , A. densiflorus , A. falcatus and A. retrofractus have also rich quantity of examined secondary metabolites as compared to commercially important species ( A. officinalis ).

Effective management and remediation strategies are crucial to minimize the impacts of both organic and inorganic contaminants on environmental quality and human health. This study investigates a novel approach utilizing cotton shell activated carbon (CSAC), rice husk activated carbon (RHAC), and wasp hive activated carbon (WHAC), produced through alkali treatment and carbonization under N 2 atmosphere at 600 °C. The adsorption capacities of biomass-derived mesoporous activated carbons (CSAC, RHAC, WHAC) alongside macroporous commercial activated carbons (CAC) were evaluated for removing rhodamine B (Rh B) and hexavalent chromium (Cr 6+ ). The CSAC exhibits remarkable adsorption efficiency (255.4 mg.g -1 ) for Cr(VI) removal, while RHAC demonstrates superior efficacy (174.2 mg . g -1 ) for Rh B adsorption. Investigating various optimal parameters including initial pH (pH 3 for Cr and pH 7 for Rh B), catalyst dosage (200 mg . L -1 ), and initial concentration (20 mg . L -1 ), the Redlich-Peterson isotherm model is applied to reveal a hybrid adsorption mechanism encompassing monolayer (chemisorption) and multilayer (van der Waals adsorption) processes. Kinetic analysis highlights the pseudo-second-order and Elovich models as the most suitable, suggesting physiochemisorption mechanisms. Thermodynamic analysis indicates the endothermic nature of the adsorption process, with increased randomness at the solid-solution interface. Isosteric heat investigations using Clausius-Clapeyron, Arrhenius, and Eyring equations reveal a heterogeneous surface nature across all activated carbons. Further confirmation of Rh B and Cr(VI) adsorption onto activated carbons is provided through FTIR, FESEM, and EDAX analysis. This study highlights the innovation and promise of utilizing biomass-derived activated carbons for effective pollutant removal., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Toxic element concentrations including As, Hg, Pb, Zn, Cr, Co, Cu, Cd, and Mn were assessed in lignite mining areas of the Kutch district of Gujarat. It was assessed mainly in land uses like reclaimed mine soil, core zone soil, roadside soil, and reference agricultural soil along the soil layer of different depths. Roadside soil has the highest concentration of mercury (5.36 mg/kg), arsenic (18.2 mg/kg), lead (34.5 mg/kg), and manganese (464 mg/kg). In comparison, the core zone soil has the highest concentration of zinc (93.4 mg/kg), chromium (52.3 mg/kg), cobalt (19.2 mg/kg), and cadmium (5.65 mg/kg), respectively. Numerous soil indices including contamination factor, geo-accumulation index, ecological risk factor (ERF), and ecological risk index (ERI) showed that the study area lies within the moderate contamination to very high contamination zone and moderately polluted to the unpolluted range. The (E i f ) (Hg) for roadside soil and core zone soil indicated high potential ecological risk category, while reclaimed mine site indicated considerable potential ecological risk. The E i f (Cd) in all sites in the mining area (121-327) can be put under high potential ecological risk, and the rest of the metals (As, Pb, Zn, Co, Cu, Cr, and Mn) can be put under low ecological risk category. In the three sites (i.e., reclaimed mine site, roadside soil, and core zone soil), core zone soil of (10-20 cm) showed the highest ERI value of 660.48 (10-20 cm), indicating high ecological risk. Cd and Hg contribute to 48% and 38% of ERI value. Hierarchical cluster analysis (HCA) suggested that the Cu and Mn were closely linked with each other and derived from similar origin and geo-chemical composition. The results of this study interpreted that the soil near the lignite mining area was contaminated with toxic elements. It is, therefore, recommended that the routine toxic element monitoring in the soil sample of the examined area should be done, and remediation action should be advised to prevent the accumulation of toxic elements in the soil and further into the food chain., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Mesenchymal stem cells (MSCs) of placental origin hold great promise in tissue engineering and regenerative medicine for diseases affecting cartilage and bone. However, their utility has been limited by their tendency to undergo premature senescence and phenotypic drift into adipocytes. This study aimed to explore the potential involvement of a specific subset of aging and antiaging genes by measuring their expression prior to and following in vitro-induced differentiation of placental MSCs into chondrocytes and osteoblasts as opposed to adipocytes. The targeted genes of interest included the various LMNA/C transcript variants (lamin A, lamin C, and lamin A∆10), sirtuin 7 (SIRT7), and SM22α, along with the classic aging markers plasminogen activator inhibitor 1 (PAI-1), p53, and p16 INK4a . MSCs were isolated from the decidua basalis of human term placentas, expanded, and then analyzed for phenotypic properties by flow cytometry and evaluated for colony-forming efficiency. The cells were then induced to differentiate in vitro into chondrocytes, osteocytes, and adipocytes following established protocols. The mRNA expression of the targeted genes was measured by RT-qPCR in the undifferentiated cells and those fully differentiated into the three cellular lineages. Compared to undifferentiated cells, the differentiated chondrocytes demonstrated decreased expression of SIRT7, along with decreased PAI-1, lamin A, and SM22α expression, but the expression of p16 INK4a and p53 increased, suggesting their tendency to undergo premature senescence. Interestingly, the cells maintained the expression of lamin C, which indicates that it is the primary lamin variant influencing the mechanoelastic properties of the differentiated cells. Notably, the expression of all targeted genes did not differ from the undifferentiated cells following osteogenic differentiation. On the other hand, the differentiation of the cells into adipocytes was associated with decreased expression of lamin A and PAI-1. The distinct patterns of expression of aging and antiaging genes following in vitro-induced differentiation of MSCs into chondrocytes, osteocytes, and adipocytes potentially reflect specific roles for these genes during and following differentiation in the fully functional cells. Understanding these roles and the network of signaling molecules involved can open opportunities to improve the handling and utility of MSCs as cellular precursors for the treatment of cartilage and bone diseases.

The activation of caspases is a crucial event and an indicator of programmed cell death, also known as apoptosis. These enzymes play a central role in cancer biology and are considered one promising target for current and future advancements in therapeutic interventions. Traditional methods of measuring caspase activity such as antibody-based methods provide fundamental insights into their biological functions, and are considered essential tools in the fields of cell and cancer biology, pharmacology and toxicology, and drug discovery. However, traditional methods, though extensively used, are now recognized as having various shortcomings. In addition, these methods fall short of providing solutions to and matching the needs of the rapid and expansive progress achieved in studying caspases. For these reasons, there has been a continuous improvement in detection methods for caspases and the network of pathways involved in their activation and downstream signaling. Over the past decade, newer methods based on cutting-edge state-of-the-art technologies have been introduced to the biomedical community. These methods enable both the temporal and spatial monitoring of the activity of caspases and their downstream substrates, and with enhanced accuracy and precision. These include fluorescent-labeled inhibitors (FLIs) for live imaging, single-cell live imaging, fluorescence resonance energy transfer (FRET) sensors, and activatable multifunctional probes for in vivo imaging. Recently, the recruitment of mass spectrometry (MS) techniques in the investigation of these enzymes expanded the repertoire of tools available for the identification and quantification of caspase substrates, cleavage products, and post-translational modifications in addition to unveiling the complex regulatory networks implicated. Collectively, these methods are enabling researchers to unravel much of the complex cellular processes involved in apoptosis, and are helping generate a clearer and comprehensive understanding of caspase-mediated proteolysis during apoptosis. Herein, we provide a comprehensive review of various assays and detection methods as they have evolved over the years, so to encourage further exploration of these enzymes, which should have direct implications for the advancement of therapeutics for cancer and other diseases.

Context: The COVID-19 (coronavirus disease 19) pandemic brought on by the SARS-CoV-2 outbreak (severe acute respiratory syndrome coronavirus 2) has stimulated the exploration of various available chemical compounds that could be used to treat the infection. This has driven numerous researchers to investigate the antiviral potential of several bioactive compounds from medicinal plants due to their reduced adverse effects compared to chemicals. Some of the bioactive compounds used in folklore treatment strategies are reported as effective inhibitors against the proliferative and infective cycles of SARS-CoV-2. The secondary metabolites from plants are generally used to treat various diseases due to their intact medicinal properties. The present study analyzes the inhibitory potential of phytochemicals from medicinal plants like Sphaeranthus indicus, Lantana camara, and Nelumbo nucifera against SARS-CoV-2 by molecular docking., Methods: Ten druggable protein targets from SARS-CoV-2 are docked against the phytochemicals from the selected medicinal plants. The phytocompounds astragalin, isoquercetin, and 5-hydroxy-7-methoxy-6-c-glycosy flavone were found to have lower binding energy depicting their inhibitive potential compared with the reported inhibitors that are used in the treatment of SARS-CoV-2 infection. The phytocompounds found to have the least binding energy were selected for further analyses. To assess the compounds' potential as drugs, their ADMET characteristics were also examined. Sphaeranthus indicus, Lantana camara, and Nelumbo nucifera six possible compounds were separately screened for ADME and toxicity characteristics; then, the results were analyzed. To assess the impact of the phytocompound binding on the dynamics of SARS-CoV-2 ribonuclease protein NSP15, microsecond-level all atomistic molecular dynamics simulations were performed, and their dynamics were analyzed. Microsecond-level molecular dynamics simulations of both the ligands complexed with NSP15 revealed that the ligand induces allosteric effects on NSP15, which could lead to destabilization of NSP15 hexameric interface and loss of RNA binding. The low binding energy exhibited by the phytochemicals from Lantana camera, Sphaeranthus indicus, and Nelumbo nucifera against the protein targets of SARS-CoV-2 showed inhibitory potential by the selected molecules. Their predicted interference of the enzymes involved in the molecular mechanisms aiding the proliferation of SARS-CoV-2 indicated the inhibitive ability of the phytochemicals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background Squamous cell carcinoma (SCC) of the maxillary alveolus and hard palate is a rare site for oral cavity carcinoma. Much controversy is there regarding the management of this site and elective neck dissection due to rarity and complex lymphatic drainage. Objective To estimate the prevalence of neck nodal metastasis in squamous cell carcinoma of maxillary alveolus and hard palate and the factors influencing the nodal metastasis. Method This retrospective cohort study includes patients diagnosed with squamous cell carcinoma of maxillary alveolus and hard palate and who underwent surgical intervention between March 2017 and March 2022. Result The study included 53 patients among them majority were men (73.6%). Prevalence of neck nodal metastasis was 36.6% and occult nodal metastasis was noted in 16%. On multivariate analysis, clinical nodal positivity increases the odds of pathological nodal positivity by 9.4 times compared to no nodal involvement (95% CI 2.07-42.57, p < 0.004). A depth of invasion (DOI) of more than 10 mm increases risk by 7.4 times for pathological nodal positivity compared to less than 10 mm invasion (95% CI 1.53- 35.27, p=0.013). Conclusion Squamous cell carcinoma of maxillary alveolus and hard palate has a high risk of nodal metastasis. Depth of invasion is an important predictor for nodal metastasis. Due to the high risk of nodal metastasis elective neck dissection would be recommended in advanced stages. Squamous cell carcinoma of maxillary alveolus and hard palate with nodal metastasis has a poor survival.

Background Human papillomavirus (HPV) infection is largely responsible for the development of invasive cervical cancer (ICC). Its prevalence, risk factors and genotype distribution among women residing in Bihar (third most populous Indian state) with and without ICC are not well known. Methods In this hospital-based study, we followed up 1439 participants with cytology and HPV report. HPV detection and genotyping were performed using the TaqMan-based real-time PCR method. Clinical and sociodemographic data were collected and analysed using statistical methods. Results The overall prevalence of HPV infection was 37.3% (537/1439) and 11 different types of HPV genotypes were observed. Higher HPV positivity was found in premalignant, intraepithelial and invasive malignant lesions of the cervix; 73.8% (93/126) of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and high-grade squamous intraepithelial lesions (HSIL) and 93.4% (114/122) of invasive malignancies were infected with HPV in comparison to only 26.1% (245/938) of negative for intraepithelial lesion or malignancy (NILM) cytology. Moreover, HPV was found in 95.2% (236/248) of histologically confirmed cases of carcinoma cervix. HPV16 and HPV18 infections were reported in 78.2% (194/248) and 8.9% (22/248), respectively. The remaining patients had infection with other high-risk strains/co-infection with multiple strains or were HPV-negative. Various socio-demographic factors including women >50 years of age, >10 years of marriage and high parity were significantly associated with HPV infection. Conclusion Our data suggest that HPV16 infection may be the major cause for ICC among women residing in Bihar. Our findings may serve as a baseline for developing an appropriate screening and vaccination strategy for Bihar.

Background: Drug-induced liver injury (DILI) is the most challenging and thought-provoking liver problem for hepatologists owing to unregulated medication usage in medical practices, nutritional supplements, and botanicals. Due to underreporting, analysis, and identification issues, clinically evaluated medication hepatotoxicity is prevalent yet hard to quantify., Purpose: This review's primary objective is to thoroughly compare pharmaceutical drugs and herbal compounds that have undergone clinical trials, focusing on their metabolic mechanisms contributing to the onset of liver illnesses and their hepatoprotective effects., Methods: The data was gathered from several online sources, such as PubMed, Scopus, Google Scholar, and Web of Science, using appropriate keywords., Results: The prevalence of conventional and herbal medicine is rising. A comprehensive understanding of the metabolic mechanism is necessary to mitigate the hepatotoxicity induced by drugs and facilitate the incorporation or substitution of herbal medicine instead of pharmaceuticals. Moreover, pre-clinical pharmacological research has the potential to facilitate the development of natural products as therapeutic agents, displaying promising possibilities for their eventual clinical implementation., Conclusions: Acetaminophen, isoniazid, rifampicin, diclofenac, and pyrogallol have been identified as the most often reported synthetic drugs that produce hepatotoxicity by oxidative stress, inflammation, apoptosis, and fibrosis during the last several decades. Due to their ability to downregulate many factors (such as cytokines) and activate several enzyme/enzyme systems, herbal substances (such as Gingko biloba extract, curcumin, resveratrol, and silymarin) provide superior protection against harmful mechanisms which induce hepatotoxicity with fewer adverse effects than their synthetic counterparts., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Lotus (Nelumbo nucifera G.) rhizomes are an under-utilized and sustainable starch source that constitutes up to 20 % starch. The review mainly focused on the extraction methods of starch, the chemical composition of LRS, and techno-functional characteristics such as swelling power, solubility, in vitro digestibility, pasting property, and gelatinization is highlighted in LRS review. Lotus rhizome starch (LRS) is also used as a water retention agent, thickening, gelling, stabilizing, and filling in food and non-food applications. Native starch has limited functional characteristics in food applications so by modifying the starch, functional characteristics are enhanced. Single and dual treatment processes are available to enhance microstructural properties, resistant starch, techno-functional, morphological, and, film-forming properties. Compared with other starch sources, there is a lack of systematic information on the LRS. Many industries are interested in developing food products based on starch such as nanoparticles, hydrogels, edible films, and many others. Additionally, there are several recommendations to improve the applications in the food industry. Finally, we provide an outlook on the future possibility of LRS., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Osteoporosis is a debilitating silent disease with a huge socio-economic impact. Prevention strategies and early detection of osteoporosis need to be carried out in every health care unit to substantially reduce the fracture rates. Indian studies have indicated a knowledge gap on diagnosis and management of osteoporosis amongst medical professionals and consumers., Areas Covered: This article reviews the evidences available on searches from PubMed and The National Library of Medicine, author's opinions based on clinical experience. There is a need for escalating the efforts to bridge the knowledge gap regarding various aspects of osteoporosis amongst professionals and consumers. Three indications for postmenopausal hormone therapy (HT), which have constantly withstood the test of time, are symptom relief, urogenital atrophy, and bone health. This article specifically focuses on management of postmenopausal osteoporosis by HT alone or in combinations., Expert Opinion: Early menopause is within 10 years of menopause and late menopause is considered beyond 10 years of menopause. HT is a cost-effective therapy in the early post menopause especially in symptomatic women at risk for osteoporosis unless contraindicated. HT prevents all osteoporotic fractures even in low-risk population. All HT preparations including low dose and non-oral routes of estrogen are effective for bone health. The bone protective effect lasts while on HT. Extended use of HT in women after 10 years of menopause with reduced bone mass is an option after detailed counselling of the risk benefit analysis compared with the other available therapies for osteoporosis. The primary therapy to prevent bone loss in women with premature menopause and secondary amenorrhea is HT. HT work up and annual follow-up is essential before prescribing HT., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Indian Orthopaedics Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Rice straw is composed of complex lignocellulosic biomass, representing a major obstacle in its conversion to bioenergy. The objective of this study was to evaluate the usefulness of less explored fungal strains Trichoderma longibrachiatum (TL) and Pycnoporus sanguineus (PS) in improving hydrolysis and bioavailability of rice straw in anaerobic digestion (AD). The fungal treatment of rice straw for 10 days by PS and TL increased biogas production by 20.79% and 17.85% and reduced soluble chemical oxygen demand (sCOD) by 71.43% and 64.70%, respectively. The AD samples containing fungal-treated rice straw showed higher lignocellulolytic enzyme activities contributing to better process performance. The taxonomic profile of microbial communities in treated samples showed increased diversity that could sustain consistent system performance and exhibit enhanced resilience against pH fluctuations. Metagenomic analysis revealed 60.82% increase in Proteobacteria in PS and 11.58% increase in Bacteroidetes in TL-treated rice straw samples resulting in improved hydrolysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quantification of the abundance and understanding of the dynamics of the microbial communities is essential to establish a basis for microbiome characterization. The conventional techniques used for the quantification of microbes are complicated and time-consuming. With scientific advancement, many techniques evolved and came into account. Among them, flow cytometry is a robust, high-throughput technique through which microbial dynamics, morphology, microbial distribution, physiological characteristics, and many more attributes can be studied in a high-throughput manner with comparatively less time and resources. Flow cytometry, when combined with other omics-based methods, offers a rapid and efficient platform to analyze and understand the composition of microbiome at the cellular level. The microbial diversity observed through flow cytometry will not be equivalent to that obtained by sequencing methods, but this integrated approach holds great potential for high throughput characterization of microbiomes. Flow cytometry is regarded as an established characterization tool in haematology, oncology, immunology, and medical microbiology research; however, its application in environmental microbiology is yet to be explored. This comprehensive review aims to delve into the diverse environmental applications of flow cytometry across various domains, including but not limited to bioremediation, landfills, anaerobic digestion, industrial bioprocesses, water quality regulation, and soil quality regulation. By conducting an in-depth analysis, this article seeks to shed light on the potential benefits and challenges associated with the utilization of flow cytometry in addressing environmental concerns., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cattle are usually raised for food, manure, leather, therapeutic, and draught purposes. Biowastes from cattle, such as dung and urine, harbor a diverse group of crucial compounds, metabolites/chemicals, and microorganisms that may benefit humans for agriculture, nutrition, therapeutics, industrial, and other utility products. Several bioactive compounds have been identified in cattle dung and urine, which possess unique properties and may vary based on agro-climatic zones and feeding practices. Therefore, cattle dung and urine have great significance, and a balanced nutritional diet may be a key to improved quality of these products/by-products. This review primarily focuses on the scientific aspects of biochemical and microbial characterization of cattle biowastes. Various methods including genomics for analyzing cattle dung and gas chromatography-mass spectroscopy for cattle urine have been reviewed. The presented information might open doors for the further characterization of cattle resources for heterogeneous applications in the production of utility items and addressing research gaps. Methods for cattle's dung and urine characterization., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic, epigenetic, and environmental variables. It is one of the world's fastest-growing diseases, with 783 million adults expected to be affected by 2045. Devastating macrovascular consequences (cerebrovascular disease, cardiovascular disease, and peripheral vascular disease) and microvascular complications (like retinopathy, nephropathy, and neuropathy) increase mortality, blindness, kidney failure, and overall quality of life in individuals with diabetes. Clinical risk factors and glycemic management alone cannot predict the development of vascular problems; multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications. In the twenty-first century, technological advancements (genome-wide association studies, next-generation sequencing, and exome-sequencing) have led to the identification of genetic variants associated with diabetes, however, these variants can only explain a small proportion of the total heritability of the condition. In this review, we address some of the likely explanations for this "missing heritability", for diabetes such as the significance of uncommon variants, gene-environment interactions, and epigenetics. Current discoveries clinical value, management of diabetes, and future research directions are also discussed., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Vaccination against COVID 19 and observing COVID appropriate behavior are effective measures to control, manage and prevent COVID-19 infection. With India starting its adolescent vaccination program, this study aimed to explore the adolescents' perception of vaccination, their COVID-appropriate behavior, compliance with two doses of COVID-19 vaccines and the experienced side effects following vaccination., Methods: A longitudinal survey was conducted among 440 adolescents visiting the COVID Vaccination Center (CVC) of a tertiary hospital in West Bengal. In the survey, adolescents were asked about family socio-demographic characteristics, their opinions on COVID-19 vaccines, and COVID-19 Appropriate Behavior (CAB) practices. Voluntary participants were given a questionnaire to fill and a telephonic interview was taken regarding side effects experienced following the vaccination and their compliance to both doses of vaccine., Results: The majority of adolescents (99.3%) had taken vaccines by their own wish. The reason for willingness to take the vaccine was the fear of being infected with COVID-19 infection (50.5%). Maximum adolescents got information regarding the COVID vaccination program through the internet (41.8%) followed by family members (30.5%). The majority of adolescents (70.9%) had a good perception of COVID-19 vaccination. A significant number of adolescents (44.8%) strongly disagreed with the statement that they don't need to follow COVID appropriate behavior after vaccination., Conclusion: The majority of adolescents had a good perception regarding COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V. on behalf of INDIACLEN.)

Cancer is a deadly disease associated with abnormal cell growth and invasion to various parts of the body. Many drugs such as cisplatin and carboplatin have been used for the treatment of cancer over the years. However, a lack of selectivity toward cancer cells and associated side effects with current treatment options has fueled continued efforts throughout the world to find better anticancer drugs. Over the past decades, copper-containing compounds have shown excellent anticancer activity. Cu(II) complexes are well studied and show broad-spectrum pharmacological activity. The redox activity of copper ions contributes to cytotoxic activity in combination with ligands that possess bioactivity. Binding of copper with various types of bidentate, tridentate, and tetradentate ligands can activate the processes of necrosis, apoptosis, and angiogenesis. Copper induces the formation of reactive oxygen species to cleave DNA. Similarly, light-assisted excitation of Cu(II) complexes in the red region of the electromagnetic spectrum helps produce different reactive species, thereby inducing anticancer activity through a photodynamic mechanism. In general, in vivo and in vitro studies have demonstrated that the administration of copper ions is effective against various cancer cell lines. Herein we discuss the past ten years of research into copper complexes of terpyridine-, 2,2'-bipyridine-, and 1,10-phenanthroline-based ligands as potential anticancer agents. The aspects of chemotherapy by redox-mediated pathways and photodynamic therapy using light-assisted excitation are reviewed, with a focus on mechanisms of activity, details of important experimental procedures, as well as drawbacks in the design of copper-containing drugs., (© 2023 Wiley-VCH GmbH.)

This paper demonstrates that some non-classical models of human decision-making can be run successfully as circuits on quantum computers. Since the 1960s, many observed cognitive behaviors have been shown to violate rules based on classical probability and set theory. For example, the order in which questions are posed in a survey affects whether participants answer 'yes' or 'no', so the population that answers 'yes' to both questions cannot be modeled as the intersection of two fixed sets. It can, however, be modeled as a sequence of projections carried out in different orders. This and other examples have been described successfully using quantum probability, which relies on comparing angles between subspaces rather than volumes between subsets. Now in the early 2020s, quantum computers have reached the point where some of these quantum cognitive models can be implemented and investigated on quantum hardware, by representing the mental states in qubit registers, and the cognitive operations and decisions using different gates and measurements. This paper develops such quantum circuit representations for quantum cognitive models, focusing particularly on modeling order effects and decision-making under uncertainty. The claim is not that the human brain uses qubits and quantum circuits explicitly (just like the use of Boolean set theory does not require the brain to be using classical bits), but that the mathematics shared between quantum cognition and quantum computing motivates the exploration of quantum computers for cognition modeling. Key quantum properties include superposition, entanglement, and collapse, as these mathematical elements provide a common language between cognitive models, quantum hardware, and circuit implementations.

In this report, synthesis, characterization, biological and molecular modeling studies of Nophen Schiff base [N,N-bis(2-hydroxy-1-naphthaldehyde)-o-phenylenediamine] and Co(II)-Nophen complex have been furnished. BSA binding affinities of the ligand and Co(II)-Nophen complex have been appraised by UV-visible, fluorescence and cyclic voltammetric techniques. Spectroscopic measurements indicate strong binding of the complex with BSA protein through static quenching mechanism with binding constant in the order of 10 4 M -1 . The negative shift of the peak potential in cyclic voltammetry suggested an electrostatic interaction. Molecular docking analysis reveals significant binding affinity (-6.3 kcal/mol) of the complex towards BSA protein. It is amazing that the in vitro cytotoxicity of Co(II)-Nophen complex against A549 cell lines (Human lung carcinoma cells) has remarkable potentials with 29 ± 1.2 µM as IC 50 value. Comparing the biological activity towards microorganisms, Co(II)-Nophen complex show substantial response than the Nophen ligand.Communicated by Ramaswamy H. Sarma.

Silver nanoparticles (AgNPs) were fabricated using Trigonella foenum-graceum L. leaf extract, belonging to the variety HM 425, as leaf extracts are a rich source of phytochemicals such as polyphenols, flavonoids, and sugars, which function as reducing, stabilizing, and capping agents in the reduction of silver ions to AgNPs. These phytochemicals were quantitatively determined in leaf extracts, and then, their ability to mediate AgNP biosynthesis was assessed. The optical, structural, and morphological properties of as-synthesized AgNPs were characterized using UV-visible spectroscopy, a particle size analyzer (PSA), FESEM (field emission scanning electron microscopy), HRTEM (high-resolution transmission electron microscopy), and FTIR (Fourier transform infrared spectroscopy). HRTEM analysis demonstrated the formation of spherically shaped AgNPs with a diameter of 4-22 nm. By using the well diffusion method, the antimicrobial potency of AgNPs and leaf extract was evaluated against microbial strains of Staphylococcus aureus, Xanthomonas spp., Macrophomina phaseolina , and Fusarium oxysporum . AgNPs showed significant antioxidant efficacy with IC 50 = 426.25 µg/mL in comparison to leaf extract with IC 50 = 432.50 µg/mL against 2,2-diphenyl-1-picrylhydrazyl (DPPH). The AgNPs (64.36 mg AAE/g) demonstrated greater total antioxidant capacity using the phosphomolybdneum assay compared to the aqueous leaf extract (55.61 mg AAE/g) at a concentration of 1100 μg/mL. Based on these findings, AgNPs may indeed be useful for biomedical applications and drug delivery systems in the future.

The aqueous Trigonella foenum-graecum L. leaf extract belonging to variety HM 444 was used as reducing agent for silver nanoparticles (AgNPs) synthesis. UV-Visible spectroscopy, Particle size analyser (PSA), Field emission scanning electron microscopy coupled to energy dispersive X-ray spectroscopy (FESEM-EDX) and High-resolution transmission electron microscopy (HRTEM) were used to characterize AgNPs. Selected area electron diffraction (SAED) confirmed the formation of metallic Ag. Fourier Transform Infrared Spectroscopy (FTIR) was done to find out the possible phytochemicals responsible for stabilization and capping of the AgNPs. The produced AgNPs had an average particle size of 21 nm, were spherical in shape, and monodispersed. It showed catalytic degradation of Methylene blue (96.57%, 0.1665 ± 0.03 min -1 ), Methyl orange (71.45%, 0.1054 ± 0.002 min -1 ), and Rhodamine B (92.72%, 0.2004 ± 0.01 min -1 ). The produced AgNPs were excellent solid bio-based sensors because they were very sensitive to Hg 2+ and Fe 3+ metal ions with a detection limit of 11.17 µM and 195.24 µM, respectively. From the results obtained, it was suggested that aqueous leaf extract demonstrated a versatile and cost-effective method and should be utilized in future as green technology for the fabrication of nanoparticles.

The ever-increasing consumption of antibiotics in both humans and animals has increased their load in municipal and pharmaceutical industry waste and may cause serious damage to the environment. Impact of antibiotics on the performance of commercially used anaerobic digesters in terms of bioenergy output, antibiotics' removal and COD removal have been compared critically with a few studies indicating >90% removal of antibiotics. AnMBR performed the best in terms of antibiotic removal, COD removal and methane yield. Most of the antibiotics investigated have adverse effects on microbiome associated with different stages and methane generation pathways of AD which has been assessed using high throughput technologies like metatranscriptomics, metaproteomics and flow cytometry. Perspectives have been given for understanding the fate and elimination of antibiotics from AD. The challenge of optimization and process improvement needs to be addressed to increase efficiency of the anaerobic digesters., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, we report the polymorphism of six coordinated Sn(IV)- tetrabromophenyl porphyrins axially armed with fluorine-substituted phenolate ligands (structural formula [Sn(TBrPP) 2+ (A - ) 2 ], where A is the axial ligand=3,5-difluoro phenol, compound 1). One form stabilizes in triclinic system (namely, 1α), and the other stabilizes in monoclinic system (namely, 1β). The two 1α and 1β polymorphs display distinct photophysical and morphological properties in the solid state. X-ray diffraction study reveals that these polymorphs 1α and 1β significantly differ in their supramolecular architecture, different axial phenolate conformations, and noncovalent interactions, which are responsible for their distinct solid-state properties. The crystal packing of these polymorphs dominates by intermolecular C-H⋅⋅⋅F, C-H⋅⋅⋅π and C-Br⋅⋅⋅F interhalogen interactions. Furthermore, the solid-state emission spectra of 1α showed red-shifted emission bands with respect to 1β, in addition the redox behavior of 1α is slightly different in comparison to 1β. Complementary theoretical studies with Hirshfeld surface analysis show the definite role of Br⋅⋅⋅F interhalogen interactions in the overall stability. Mapping the electrostatic potential isosurfaces with the aid of density functional theory in compound 1 clearly shows the presence of σ-hole, a requisite feature to show halogen interactions in the crystalline state. In addition, lattice energy and single point energy calculation shows that 1α was found to be energetically more favorable and thermodynamically more stable compare to 1β., (© 2022 Wiley-VCH GmbH.)

Background & Objectives: A successful blood meal acquisition process by an adult female mosquito is accomplished through salivary glands, which releases a cocktail of proteins to counteract the vertebrate host's immune homeostasis. Here, we characterize a salivary-specific Heme peroxidase family member HPX12, originally identified from Plasmodium vivax infected salivary RNAseq data of the mosquito Anopheles stephensi., Methods: To demonstrate we utilized a comprehensive in silico and functional genomics approach., Results: Our dsRNA-mediated silencing experiments demonstrate that salivary AsHPX12 may regulate pre-blood meal-associated behavioral properties such as probing time, probing propensity, and host attraction. Altered expression of the salivary secretory and antennal proteins expression may have accounted for salivary homeostasis disruption resulting in the unusual fast release of salivary cocktail proteins and delayed acquisition of blood meal in the AsHPX12 knockdown mosquitoes. We also observed a significant parallel transcriptional modulation in response to blood feeding and P. vivax infection., Interpretation & Conclusion: With this work, we establish a possible functional correlation of AsHPX12 role in the maintenance of salivary physiological-homeostasis, and Plasmodium sporozoites survival/transmission, though the mechanism is yet to unravel., Competing Interests: None

The periodic ingestion of a protein-rich blood meal by adult female mosquitoes causes a drastic metabolic change in their innate physiological status, which is referred to as a 'metabolic switch'. While understanding the neural circuits for host-seeking is modestly attended, how the gut 'metabolic switch' modulates brain functions, and resilience to physiological homeostasis, remains unexplored. Here, through a comparative brain RNA-Seq study, we demonstrate that the protein-rich diet induces the expression of brain transcripts related to mitochondrial function and energy metabolism, possibly causing a shift in the brain's engagement to manage organismal homeostasis. A dynamic mRNA expression pattern of neuro-signaling and neuro-modulatory genes in both the gut and brain likely establishes an active gut-brain communication. The disruption of this communication through decapitation does not affect the modulation of the neuro-modulator receptor genes in the gut. In parallel, an unusual and paramount shift in the level of neurotransmitters (NTs), from the brain to the gut after blood feeding, further supports the idea of the gut's ability to serve as a 'second brain'. After blood-feeding, a moderate enrichment of the gut microbial population, and altered immunity in the gut of histamine receptor-silenced mosquitoes, provide initial evidence that the gut-microbiome plays a crucial role in gut-brain-axis communication. Finally, a comparative metagenomics evaluation of the gut microbiome highlighted that blood-feeding enriches the family members of the Morganellaceae and Pseudomonadaceae bacterial communities. The notable observation of a rapid proliferation of Pseudomonas bacterial sp. and tryptophan enrichment in the gut correlates with the suppression of appetite after blood-feeding. Additionally, altered NTs dynamics of naïve and aseptic mosquitoes provide further evidence that gut-endosymbionts are key modulators for the synthesis of major neuroactive molecules. Our data establish a new conceptual understanding of microbiome-gut-brain-axis communication in mosquitoes.

Introduction: Agad Tantra being the unique branch that deals with toxicology and its management enlists several antitoxic drugs used for various poisonings. Ancient texts comprise the list of a wide range of traditional medicines, but they are not explored due to lack of incomprehension., Aims: The review has been written with the aim to dig out the hidden knowledge of Vishaghna Dravyas (alexeterics) mentioned in Kaiydeva Nighantu., Materials and Methods: This Nighantu was written in the 15 th century A. D. by Kaiydeva with the name " Pathya - Apathya - Vibodhaka" it comprising of total 514 Dravyas out of which 175 drugs possess Vishagna (anti-poisonous) property., Results: These Vishaghna Dravyas (alexeterics) have been distributed based on various Vargas (classes) which is described as 121 belonging to Ausghada Varga (drug class) as single drugs and four as groups, total of 16 from Dhatu Varga (metal class) as single drugs and one as compound or as a group, 9 from Dhanya Varga (cereal class) as a single drug, 15 in Dravya Varga as single drugs, and 5 as compound or as a group. Two each in Kritana Varga and Vihara Varga and one in Mansa Varga as compound or as a group. Out of all the 175 Vishagna Dravayas (alexeterics), 18 Dravyas (substances) are specific indications in combating particular types of envenomation or poisoning conditions., Conclusion: All the abovementioned drugs are screened for the purpose of revalidation to bring out their therapeutic utility., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 AYU (An International Quarterly Journal of Research in Ayurveda).)

Background: Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. Transferrins are glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes., Results: We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. culicifacies. A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation., Conclusion: All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome., Competing Interests: the authors have declared that no competing interests exist.

In vertebrates dysregulation of the antioxidant defense system has a detrimental impact on male fertility and reproductive physiology. However, in insects, especially mosquitoes the importance of sperm quality has been poorly studied. Since long-term storage of healthy and viable sperm earmarks male reproductive competency, we tested whether the heme peroxidase, a member of antioxidant enzyme family proteins, and abundantly expressed in the testis, also influence male fertility in the mosquito An. stephensi. Here, we show that a heme peroxidase 12 (HPX12), is an important cellular factor to protect the sperms from oxidative stress, and maintains semen quality in the male mosquito reproductive organ. We demonstrate that knockdown of the HPX12 not only impairs the sperm parameters such as motility, viability but also causes a significant down-regulation of MAG expressing transcripts such as ASTEI02706, ASTEI00744, ASTEI10266, likely encoding putative Accessory gland proteins. Mating with HPX12 knockdown male mosquitoes, resulted in ~ 50% reduction in egg-laying, coupled with diminished larval hatchability of a gravid female mosquito. Our data further outlines that increased ROS in the HPX12 mRNA depleted mosquitoes is the ultimate cause of sperm disabilities both qualitatively as well as quantitatively. Our data provide evidence that testis expressing AsHPX12 is crucial for maintaining optimal homeostasis for storing and protecting healthy sperms in the male mosquito's reproductive organs. Since, high reproductive capacity directly influences the mosquito population, manipulating male mosquito reproductive physiology could be an attractive tool to combat vector-borne diseases., (© 2022. The Author(s).)

Background and study aims  Killian-Jamieson Diverticulum (KJD) is a rarer and more recently described upper pharyngeal diverticulum than Zenker's diverticulum (ZD). KJD is more difficult to manage than ZD because it tends to extend lower into the upper mediastinum and the diverticulum neck is in close proximity to the recurrent laryngeal nerve. There is limited literature on KJD management and transcervical surgical diverticulectomy is the mainstay of therapy. Patients and methods  Here we describe two methods of endoscopic diverticulotomy to treat KJD - direct and tunneling diverticulotomy (with hypopharyngeal tunnel or ultra-short tunnel - the latter being our preferred technique). Results  This was a retrospective study including 13 consecutive patients between March 2015 and April 2018. Three patients received direct and 10 received tunneling diverticulotomy (7 with the hypopharyngeal tunnel and 3 with the ultra-short tunnel). All procedures were completed in 16 to 52 minutes. There was no incidence of bleeding, mediastinitis, or sign of recurrent laryngeal nerve injury. At follow up of 9 to 79 months (median 33), the clinical success rate was 92 % (12/13); 11 patients had complete symptom resolution (post-operative symptom score = 0) and one patient had near-complete symptom resolution (occasional residual dysphagia). One patient receiving direct myotomy had limited symptom relief (frequent residual dysphagia and occasional residual regurgitation), possibly related to incomplete myotomy. Conclusions  Endoscopic tunneling diverticulotomy is a feasible, safe, and effective method to treat KJD., Competing Interests: Competing interests Dr. Stavropoulos is a consultant for Boston Scientific and Olympus and receives honoraria from ERBE USA., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Cutaneous Adverse Drug Reactions (ADRs) are common and pose a serious challenge to physicians, especially in cases when the patient has many comorbidities, is polypharmacy, or self-administers over-the-counter medications., Objective: The objective of this study is to analyze the clinical pattern and incidence of cutaneous ADRs and perform causality assessment using the WHO-UMC scale and Naranjo's scale. The severity of the reactions was determined by the Hartwig scale., Methods: This was conducted as a prospective observational study in patients admitted to SRM Medical College, Kattankulathur, Tamil Nadu, India, between November 2016 to August 2018 after obtaining Institutional Ethics Committee clearance of all adverse drug reactions reported at the hospital., Results: Of the 158 ADRs reported during the time period, 101 were cutaneous ADRs, of which the most common presentation was maculopapular rash (n=42; 41.58%). The most common drugs which produced cutaneous adverse reactions were antimicrobials (n=58; 57.42%) followed by NSAIDs (n=35; 34.6%). The causality assessment as per the Naranjo scale yielded 3.96% (4) cases as definite, 81.18% (82) as probable, and 14.85% (15) as possible, whereas the WHO scale yielded 9 (89.10%) certain, 64 (63.36%) probable and 28 (27.72%) possible cases. The severity of the cases determined as per the Hartwig scale yielded 82.17% cases as mild and 17.82% as moderate., Conclusion: It is important to recognise the ADRs at the right time and exert caution in future use. This can minimise harm to the patient both physically and financially and improve the outcome of the treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Dengue fever has become one of the deadliest infectious diseases and requires the development of effective antiviral therapies. It is caused by members of the Flaviviridae family, which also cause various infections in humans, including dengue fever, tick-borne encephalitis, West Nile fever, and yellow fever. In addition, since 2019, dengue-endemic regions have been grappling with the public health and socio-economic impact of the ongoing coronavirus disease 19. Co-infections of coronavirus and dengue fever cause serious health complications for people who also have difficulty managing them. To identify the potentials of mangiferin, a molecular docking with various dengue virus proteins was performed. In addition, to understand the gene interactions between human and dengue genes, Cytoscape was used in this research. The Kyoto Encyclopedia of Genes and Genomes software was used to find the paths of Flaviviridae. The Kyoto Encyclopedia of Genes and Genomes and the Reactome Pathway Library were used to understand the biochemical processes involved. The present results show that mangiferin shows efficient docking scores and that it has good binding affinities with all docked proteins. The exact biological functions of type I interferon, such as interferon-α and interferon-β, were also shown in detail through the enrichment analysis of the signaling pathway. According to the docking results, it was concluded that mangiferin could be an effective drug against the complications of dengue virus 1, dengue virus 3, and non-structural protein 5. In addition, computational biological studies lead to the discovery of a new antiviral bioactive molecule and also to a deeper understanding of viral replication in the human body. Ultimately, the current research will be an important resource for those looking to use mangiferin as an anti-dengue drug., Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-022-00258-6., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia 2022.)

In type 2 diabetes mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to tuberculosis (TB) and result in poor TB control. Here, an integrative pathway-based approach is used to investigate perturbed pathways in T2DM patients that render susceptibility to TB. We obtained 36 genes implicated in type 2 diabetes-associated tuberculosis (T2DMTB) from the literature. Gene expression analysis on T2DM patient data (GSE26168) showed that DEFA1 is differentially expressed at P adj <0.05. The human host TB susceptibility genes TNFRSF10A, MSRA, GPR148, SLC37A3, PXK, PROK2, REV3L, PGM1, HIST3H2A, PLAC4, LETM2, and EMP2 and hsa-miR-146a microRNA were also differentially expressed at P adj <0.05. We included all these genes and added the remaining 28 genes from the T2DMTB set and the remaining differentially expressed genes at P adj <0.05 in STRING and obtained a well-connected network with high confidence score (≥0.7). Further, we extracted the KEGG pathways at FDR <0.05 and retained only the diabetes and TB pathways. The network was simulated with BioNSi using gene expression data. It is evident from BioNSi analysis that the NF-kappa B and Toll-like receptor pathways are commonly perturbed with high ranking in multiple gene expression datasets of type 2 diabetes versus healthy controls. The other pathways, necroptosis pathway and FoxO signalling pathway, appear perturbed with high ranking in different gene expression datasets. These pathways likely underlie susceptibility to TB in T2DM patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal loss to human health and lives and has deeply impacted socio-economic growth. Remarkable efforts have been made by the scientific community in containing the virus by successful development of vaccines and diagnostic kits. Initiatives towards drug repurposing and discovery have also been undertaken. In this study, we compiled the known natural anti-viral compounds using text mining of the literature and examined them against four major structural proteins of SARS-CoV-2, namely, spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein. Following computational approaches, we identified fangchinoline and versicolactone C as the compounds to exhibit strong binding to the target proteins and causing structural deformation of three structural proteins (N, S and M). We recommend the inhibitory effects of these compounds from our study should be experimentally validated against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Background and Aims: Peroral endoscopic myotomy (POEM) is becoming the treatment of choice for achalasia. Data beyond 3 years are emerging but are limited. We herein report our 10-year experience, focusing on long-term efficacy and safety including the prevalence, management, and sequelae of postoperative reflux., Methods: This was a single-center prospective cohort study., Results: Six hundred ten consecutive patients received POEM from October 2009 to October 2019, 160 for type 1 achalasia (26.2%), 307 for type II (50.3%), 93 for type III (15.6%), 25 for untyped achalasia (4.1%), and 23 for nonachalasia disorders (3.8%). Two hundred ninety-two patients (47.9%) had prior treatment(s). There was no aborted POEM. Median operation time was 54 minutes. Accidental mucosotomies occurred in 64 patients (10.5%) and clinically significant adverse events in 21 patients (3.4%). No adverse events led to death, surgery, interventional radiology interventions/drains, or altered functional status. At a median follow-up of 30 months, 29 failures occurred, defined as postoperative Eckardt score >3 or need for additional treatment. The Kaplan-Meier clinical success estimates at years 1, 2, 3, 4, 5, 6, and 7 were 98%, 96%, 96%, 94%, 92%, 91%, and 91%, respectively. These are highly accurate estimates because only 13 patients (2%) were missing follow-up assessments. One hundred twenty-five patients (20.5%) had reflux symptoms more than once per week. At a median of 4 months, the pH study was completed in 406 patients (66.6%) and was positive in 232 (57.1%), and endoscopy was completed in 438 patients (71.8%) and showed reflux esophagitis in 218 (49.8%), mostly mild., Conclusions: POEM is exceptionally safe and highly effective on long-term follow-up, with >90% clinical success at ≥5 years., (Copyright © 2021. Published by Elsevier Inc.)

Anopheles stephensi and Anopheles culicifacies are dominant malarial vectors in urban and rural India, respectively. Both species carry significant biological differences in their behavioral adaptation and immunity, but the genetic basis of these variations are still poorly understood. Here, we uncovered the genetic differences of immune blood cells, that influence several immune-physiological responses. We generated, analyzed and compared the hemocyte RNA-Seq database of both mosquitoes. A total of 5,837,223,769 assembled bases collapsed into 7,595 and 3,791 transcripts, originating from hemocytes of laboratory-reared 3-4 days old naïve (sugar-fed) mosquitoes, Anopheles stephensi and Anopheles culicifacies respectively. Comparative GO annotation analysis revealed that both mosquito hemocytes encode similar proteins. Furthermore, while An. stephensi hemocytes showed a higher percentage of immune transcripts encoding APHAG (Autophagy), IMD (Immune deficiency pathway), PRDX (Peroxiredoxin), SCR (Scavenger receptor), IAP (Inhibitor of apoptosis), GALE (galactoside binding lectins), BGBPs (1,3 beta D glucan binding proteins), CASPs (caspases) and SRRP (Small RNA regulatory pathway), An. culicifacies hemocytes yielded a relatively higher percentage of transcripts encoding CLIP (Clip domain serine protease), FREP (Fibrinogen related proteins), PPO (Prophenol oxidase), SRPN (Serpines), ML (Myeloid differentiation 2-related lipid recognition protein), Toll path and TEP (Thioester protein), family proteins. However, a detailed comparative Interproscan analysis showed An. stephensi mosquito hemocytes encode proteins with increased repeat numbers as compared to An. culicifacies. Notably, we observed an abundance of transcripts showing significant variability of encoded proteins with repeats such as LRR (Leucine rich repeat), WD40 (W-D dipeptide), Ankyrin, Annexin, Tetratricopeptide and Mitochondrial substrate carrier repeat-containing family proteins, which may have a direct influence on species-specific immune-physiological responses. Summarily, our deep sequencing analysis unraveled that An. stephensi evolved with an expansion of repeat sequences in hemocyte proteins as compared to An. culicifacies, possibly providing an advantage for better adaptation to diverse environments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite the recent advancements in therapeutics and personalized medicine, breast cancer remains one of the most lethal cancers among women. The prognostic and diagnostic aids mainly include assessment of tumor tissues with conventional methods towards better therapeutic strategies. However, current era of gene-based research may influence the treatment outcome particularly as an adjunct to diagnostics by exploring the role of non-invasive liquid biopsies or circulating markers. The characterization of tumor milieu for physiological fluids has been central to identifying the role of exosomes or small extracellular vesicles (sEVs). These exosomes provide necessary communication between tumor cells in the tumor microenvironment (TME). The manipulation of exosomes in TME may provide promising diagnostic/therapeutic strategies, particularly in triple-negative breast cancer patients. This review has described and highlighted the role of exosomes in breast carcinogenesis and how they could be used or targeted by recent immunotherapeutics to achieve promising intervention strategies.

Background: The acetate ion has important physiological functions and important therapeutic applications. A rapid LC-MS/MS method is described to measure acetate ions in human plasma without chemical derivatization. Materials & methods: A 200 μl sample was spiked with the internal standard 1,2- 13 C-acetate and proteins precipitated with trichloroacetic acid. The supernatant was recovered and separated under acidic conditions on a C18-column. The eluent was alkalinized by post-column infusion of methanolic ammonium hydroxide. Acetate ions were monitored on a low resolution mass spectrometer in negative ion mode. Results: Method was validated for accuracy and precision with a lower limit of quantitation of 9.7 μM and linear dynamic range up to 339.6 μM. Conclusion: The method is open for analytical improvement and adapts with metabolomic and pharmacometabolomic studies on chemicals of similar nature.

Competing Interests: None