Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Microbial oases in the ice: A state-of-the-art review on cryoconite holes as diversity hotspots and their scientific connotations.

Cryoconite holes, small meltwater pools on the surface of glaciers and ice sheets, represent extremely cold ecosystems teeming with diverse microbial life. Cryoconite holes exhibit greater susceptibility to the impacts of climate change, underlining the imperative nature of investigating microbial communities as an essential module of polar and alpine ecosystem monitoring efforts. Microbes in cryoconite holes play a critical role in nutrient cycling and can produce bioactive compounds, holding promise for industrial and pharmaceutical innovation. Understanding microbial diversity in these delicate ecosystems is essential for effective conservation strategies. Therefore, this review discusses the microbial diversity in these extreme environments, aiming to unveil the complexity of their microbial communities. The current study envisages that cryoconite holes as distinctive ecosystems encompass a multitude of taxonomically diverse and functionally adaptable microorganisms that exhibit a rich microbial diversity and possess intricate ecological functions. By investigating microbial diversity and ecological functions of cryoconite holes, this study aims to contribute valuable insights into the broader field of environmental microbiology and enhance further understanding of these ecosystems. This review seeks to provide a holistic overview regarding the formation, evolution, characterization, and molecular adaptations of cryoconite holes. Furthermore, future research directions and challenges underlining the need for long-term monitoring, and ethical considerations in preserving these pristine environments are also provided. Addressing these challenges and resolutely pursuing future research directions promises to enrich our comprehension of microbial diversity within cryoconite holes, revealing the broader ecological and biogeochemical implications. The inferences derived from the present study will provide researchers, ecologists, and policymakers with a profound understanding of the significance and utility of cryoconite holes in unveiling the microbial diversity and its potential applications.

Anterior pituitary hormone dysfunction among individuals with complete heart block requiring pacemaker.

Background & objectives Neuronal hypoxia associated with conditions like traumatic brain injury and cardiac tachyarrhythmia has been implicated in causing hypopituitarism. Individuals with complete heart block (CHB) may be predisposed to develop anterior pituitary hormone dysfunction in the long term. The objective of this study was to investigate anterior pituitary hormone functions in individuals after CHB. Methods This prospective cohort study included 30 individuals (21 men and 9 women) with CHB requiring pacemaker implantation, who were evaluated at admission and then at a mean follow up of 12.4 ± 2.2 months to look for development of any degree of hypopituitarism. In addition to the measurement of hormones like follicle-stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), total tetra iodothyronines (TT4), free tetraiodothyronines (FT4), cortisol, insulin-like growth factor-1 (IGF-1), testosterone and estradiol, a fixed-dose glucagon stimulation test (GST) was performed to assess growth hormone (GH) and adrenocorticotrophic hormone (ACTH) axis. Results The mean age of the participants was 64.9 ± 11.3 yr. At follow up evaluation, 17 (56.7%) had low serum IGF-1, and among them, seven (23%) had growth hormone deficiency (GHD) (peak GH <1.0 ng/ml after GST). Six participants (20%) had ACTH deficiency (peak cortisol <9 ug/dl after GST) and one had TSH deficiency. None had prolactin (PRL) or gonadotropin deficiency. Overall, hormone deficiencies were observed in nine patients (30%). Interpretation & conclusions This pilot study detected loss of anterior pituitary hormones in a significant number of individuals of CHB at 12 months follow up. Unrecognised hypopituitarism may have resulted in significant morbidity and mortality in these individuals.

Candidaemia and Central Line-Associated Candidaemia in a Network of Indian ICUs: Impact of COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Candidaemia is a potentially life-threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare-associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID-19 had on the rates and associated mortality of candidaemia. METHODS: This study included adult patients from 67 Indian ICUs in the AIIMS-HAI surveillance network that conducted BSI surveillance in COVID-19 and non-COVID-19 ICUs during and before the COVID-19 pandemic periods. Hospitals identified healthcare-associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. RESULTS: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID-19 ICUs (2.52/1000 patient days) was significantly higher than in non-COVID-19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID-19 ICUs (4.53/1000 central line days) was also significantly higher than in non-COVID-19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID-19 ICUs associated with candidaemia (61%) was higher than that in non-COVID-19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. CONCLUSION: Patients in ICUs with COVID-19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country.

Hypermethylation and down-regulation of vitamin D receptor (VDR) as contributing factors for polycystic ovary syndrome (PCOS): a case-control study from Kashmir, North India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a prevailing endocrinopathy affecting a significant population of women of reproductive age across the globe. A myriad set of complex intertwined factors ranging from etiological, genetic, and epigenetic reasons cause this disorder. Out of the different factors, vitamin D shows an imperative aspect in health and fertility of women with polycystic ovary syndrome (PCOS). The importance of vitamin D is facilitated by vitamin D receptor (VDR), a ligand-dependent transcription factor in the steroid/ thyroid hormone receptor superfamily that controls the pleiotropic biological properties of vitamin D. PURPOSE: The purpose of this study was to evaluate the role of promoter methylation of the VDR gene, a transcription factor with numerous biological utilities, with its relative expression and clinico-pathological findings and outcomes. METHODOLOGY: A total of 200 blood samples were collected, 100 from PCOS case subjects, and 100 from the normal healthy controls respectively, which were assessed by qRT-PCR for determining the expression summary. MS-PCR technique was used for analyzing the promoter methylation status of the VDR gene. Blood samples were withdrawn, respectively, for each case and the control study separately experimented for different stages for the given study, of which estimation of vitamin D was also a part. RESULTS: In this test-versus-control study, first, the promoter methylation status of VDR gene was identified which was found more prominent i.e., hyper-methylation of the VDR gene was identified in 84 cases (84%), and in the normal healthy controls, it was found (62%). The promoter methylation status of the VDR gene has remarkably shown the results with a significant difference (p value < 0.0001*). Second, the expression analysis of VDR gene was found to be strongly downregulated in majority (64%) of PCOS case samples analyzed by means fold change of 0.8743 (± 0.06466) (p value 0.0054**). This result is, therefore, indicative of VDR gene role in PCOS pathogenesis as the said gene is downregulated. Moreover, compared to the vitamin D parameter, hyper-methylation and expression analysis of the VDR promoter gene were found to correspond to some associations with PCOS. Certain case-and-control study analyses showed that patients with normal vitamin D levels showed less indicative effects of PCOS and vice versa. CONCLUSION: Our study, being exclusive from Kashmir, one of the foremost specified that VDR confirms anomalous methylation configuration in PCOS with subsequent downregulation in the gene expression i.e., there is an inverse correlation among VDR gene expression (downregulated) and methylation status (hyper-methylated) from the conclusion of our PCOS case-versus-control study.

Correlation of Diabetes Related Factors with Vitamin D and Immunological Parameters in T2DM Kashmiri Population.

In this study, the role of inflammatory biomarkers and vitamin D in Type 2 diabetes mellitus (T2DM) and their correlation with diabetes related factors (HbA1c, FPG, and insulin) was analysed. In this study, Kashmiri patients with T2DM and healthy individuals were considered as cases (n = 100) and controls (n = 100) respectively. Blood samples from both groups were collected, inflammatory biomarkers (TNF-α, CRP), as well as serum vitamin D levels, were estimated by ELISA. From our results it was revealed that patients with T2DM had significantly lower serum vitamin D levels than control groups (p<0.05). Pro-inflammatory cytokine levels, including TNF-α and CRP, were seen to be elevated reaching a level of statistical significance (p<0.05). On correlating the HbA1c, FPG and insulin with TNF-α, CRP and vitamin D, significant positive correlation (p<0.05) was found between TNF-α and CRP with HbA1c and FPG in patients, non-significant positive correlation (p>0.05) was observed between insulin with TNF-α, and vitamin D and weak negative correlation with CRP in case study group. On correlating the impact of vitamin D on HbA1c and FPG levels, non-significant weak negative correlation was observed in patient group than controls, indicating that patients with lower vitamin D levels have higher HbA1c, showing that lower vitamin D have some role in etiology of T2DM.

Molecular Mechanisms in the Etiology of Polycystic Ovary Syndrome (PCOS): A Multifaceted Hypothesis Towards the Disease with Potential Therapeutics.

Among the premenopausal women, Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrinopathy affecting the reproductive system and metabolic rhythms leading to disrupted menstrual cycle. Being heterogeneous in nature it is characterized by complex symptomology of oligomennorhoea, excess of androgens triggering masculine phenotypic appearance and/or multiple follicular ovaries. The etiology of this complex disorder remains somewhat doubtful and the researchers hypothesize multisystem links in the pathogenesis of this disease. In this review, we attempt to present several hypotheses that tend to contribute to the etiology of PCOS. Metabolic inflexibility, aberrant pattern of gonadotropin signaling along with the evolutionary, genetic and environmental factors have been discussed. Considered a lifelong endocrinological implication, no universal treatment is available for PCOS so far however; multiple drug therapy is often advised along with simple life style intervention is mainly advised to manage its cardinal symptoms. Here we aimed to present a summarized view of pathophysiological links of PCOS with potential therapeutic strategies.

Microbiome dysbiosis and epigenetic modulations in lung cancer: From pathogenesis to therapy.

The lung microbiome plays an essential role in maintaining healthy lung function, including host immune homeostasis. Lung microbial dysbiosis or disruption of the gut-lung axis can contribute to lung carcinogenesis by causing DNA damage, inducing genomic instability, or altering the host's susceptibility to carcinogenic insults. Thus far, most studies have reported the association of microbial composition in lung cancer. Mechanistic studies describing host-microbe interactions in promoting lung carcinogenesis are limited. Considering cancer as a multifaceted disease where epigenetic dysregulation plays a critical role, epigenetic modifying potentials of microbial metabolites and toxins and their roles in lung tumorigenesis are not well studied. The current review explains microbial dysbiosis and epigenetic aberrations in lung cancer and potential therapeutic opportunities.

Unraveling the potential of environmental DNA for deciphering recent advances in plant-animal interactions: a systematic review.

MAIN CONCLUSION: Environmental DNA-based monitoring provides critical insights for enhancing our understanding of plant-animal interactions in the context of worldwide biodiversity decrease for developing a global framework for effective plant biodiversity conservation. To understand the ecology and evolutionary patterns of plant-animal interactions (PAI) and their pivotal roles in ecosystem functioning advances in molecular ecology tools such as Environmental DNA (eDNA) provide unprecedented research avenues. These methods being non-destructive in comparison to traditional biodiversity monitoring methods, enhance the discernment of ecosystem health, integrity, and complex interactions. This review intends to offer a systematic and critical appraisal of the prospective of eDNA for investigating PAI. The review thoroughly discusses and analyzes the recent reports (2015-2022) employing preferred reporting items for systematic reviews and meta-analyses (PRISMA) to outline the recent progression in eDNA approaches for elucidating PAI. The current review envisages that eDNA has a significant potential to monitor both plants and associated cohort of prospective pollinators (avian species and flowering plants, bees and plants, arthropods and plants, bats and plants, etc.). Furthermore, a brief description of the factors that influence the utility and interpretation of PAI eDNA is also presented. The review establishes that factors such as biotic and abiotic, primer selection and taxonomic resolution, and indeterminate spatio-temporal scales impact the availability and longevity of eDNA. The study also identified the limitations that influence PAI detection and suggested possible solutions for better execution of these molecular approaches. Overcoming these research caveats will augment the assortment of PAI analysis through eDNA that could be vital for ecosystem health and integrity. This review forms a critical guide and offers prominent insights for ecologists, environmental managers and researchers to assess and evaluate plant-animal interaction through environmental DNA.

High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome-A case-control study.

OBJECTIVE: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10-year probability of cardiovascular (CV) events in SS patients. DESIGN: Case-control study Sixty-three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity-matched controls. MEASUREMENTS: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16-row multislice computed tomography scanner. RESULTS: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi-Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294). CONCLUSION: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.

Molecular characterization of fungal endophyte diversity isolated from Aconitum heterophyllum: a critically endangered medicinal plant of Kashmir Himalaya.

Aconitum heterophyllum is a rare perennial herb from Kashmir Himalayas. Due to its threatened status and dependence on its environment, the plant was examined for any potential endophytes, which is of utmost importance for bioprospection. In the current study, endophytic fungal diversity associated with A. heterophyllum was examined, and 328 fungal isolates were found in the plant's leaf, stem, and root tissues. Twelve (12) endophytic fungal species were identified utilizing, molecular analysis of the nuclear ribosomal DNA Internal Transcribes Spacer (ITS), rLSU, and rSSU sequences. Maximum likelihood analysis was used to determine the phylogenetic connection between each isolate. The genera Arthrinium, Chaetomium, Purpureocillium, Alternaria, Penicillium, Aspergillus, Cladosporium, and Bjerkandera species dominated the ascomycete and basidiomycete fungal endophytes.

Best practice approach for redo-surgeries after sleeve gastrectomy, an expert's modified Delphi consensus.

BACKGROUND: Sleeve gastrectomy (SG) is the most common metabolic and bariatric surgical (MBS) procedure worldwide. Despite the desired effect of SG on weight loss and remission of obesity-associated medical problems, there are some concerns regarding the need to do revisional/conversional surgeries after SG. This study aims to make an algorithmic clinical approach based on an expert-modified Delphi consensus regarding redo-surgeries after SG, to give bariatric and metabolic surgeons a guideline that might help for the best clinical decision. METHODS: Forty-six recognized bariatric and metabolic surgeons from 25 different countries participated in this Delphi consensus study in two rounds to develop a consensus on redo-surgeries after SG. An agreement/disagreement ≥ 70.0% on statements was considered to indicate a consensus. RESULTS: Consensus was reached for 62 of 72 statements and experts did not achieve consensus on 10 statements after two rounds of online voting. Most of the experts believed that multi-disciplinary team evaluation should be done in all redo-procedures after SG and there should be at least 12 months of medical and supportive management before performing redo-surgeries after SG for insufficient weight loss, weight regain, and gastroesophageal reflux disease (GERD). Also, experts agreed that in case of symptomatic GERD in the presence of adequate weight loss, medical treatment for at least 1 to 2 years is an acceptable option and agreed that Roux-en Y gastric bypass is an appropriate option in this situation. There was disagreement consensus on efficacy of omentopexy in rotation and efficacy of fundoplication in the presence of a dilated fundus and GERD. CONCLUSION: Redo-surgeries after SG is still an important issue among bariatric and metabolic surgeons. The proper time and procedure selection for redo-surgery need careful considerations. Although multi-disciplinary team evaluation plays a key role to evaluate best options in these situations, an algorithmic clinical approach based on the expert's consensus as a guideline can help for the best clinical decision-making.

Bariatric and metabolic surgery in patients with low body mass index: an online survey of 543 bariatric and metabolic surgeons.

BACKGROUND: Metabolic and bariatric surgery (MBS) in patients with low body mass index patients is a topic of debate. This study aimed to address all aspects of controversies in these patients by using a worldwide survey. METHODS: An online 35-item questionnaire survey based on existing controversies surrounding MBS in class 1 obesity was created by 17 bariatric surgeons from 10 different countries. Responses were collected and analysed by authors. RESULTS: A total of 543 bariatric surgeons from 65 countries participated in this survey. 52.29% of participants agreed with the statement that MBS should be offered to class-1 obese patients without any obesity related comorbidities. Most of the respondents (68.43%) believed that MBS surgery should not be offered to patients under the age of 18 with class I obesity. 81.01% of respondents agreed with the statement that surgical interventions should be considered after failure of non-surgical treatments. CONCLUSION: This survey demonstrated worldwide variations in metabolic/bariatric surgery in patients with class 1 obesity. Precise analysis of these results is useful for identifying different aspects for future research and consensus building.

Characterization and adsorption of malachite green dye from aqueous solution onto Salix alba L. (Willow tree) leaves powder and its respective biochar.

In the present study, the use of low-cost, highly efficient, eco-friendly, and abundantly available (in Kashmir region, J&K India) willow leaves from which adsorbents like willow leaves powder (WLP) and willow leaves biochar (WLB) were prepared, have been found to be efficient for malachite green (MG) dye removal and can be used as an alternative to the current expensive methods of removing the same dye from an aqueous solution. The techniques like Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and carbon, hydrogen, nitrogen, sulphur (CHNS) analyser were used to characterize the samples without any chemical treatment. SEM of the adsorbents shows the presence of different sized pores, cracks, and crevices. FTIR and CHNS show functional groups and elemental concentration, respectively. The effects of various experimental parameters such as contact time, adsorbent dosage, initial dye concentration, salt treatment, and pH were investigated and optimal experimental conditions were obtained. It has been found that Langmuir, Freundlich, and Temkin isotherms were useful for describing the equilibrium of adsorption system. The equilibrium adsorption data in this research work was found to follow both Langmuir and Freundlich isotherm models and maximum monolayer capacity of WLP and WLB were found to be 10.014 and 21.244 mg/g, respectively. The experimental data for both WLP and WLB followed pseudo-second-order kinetic model with R2= 0.999. Intraparticle diffusion model reveals that more than one mechanism influenced the adsorption process. Thermodynamic study concluded that the adsorption is spontaneous for both adsorbents but exothermic for WLP and is endothermic in nature for WLB. Present exploration and comparison with other reported adsorbents concluded that, WLP and WLB may be useful as low-cost attractive option for the removal of MG dye from aqueous solution and therefore, also from wastewater containing MG dye.

This study reports for the first time the use of Salix alba L. (Willow tree) leaves and its biochar as the adsorbents for the removal of malachite green dye from its aqueous solution.Both the adsorbents namely willow leaves powder (WLP) and willow leaves biochar (WLB) are rapid and highly efficient for MG dye removal having percentage removal more than 92.5%.For WLB adsorbent the percentage removal crosses 98.5% by the addition of 0.2 g KCl and by increasing 40 °C temperatures.The adsorbents used in this research work are comparable with the highly efficient low-cost adsorbents used for MG dye like rice husk, water hyacinth, seaweed, etc. found in the literature.The adsorbents (WLP and WLB) were used without chemical treatment having good removal efficiency, cheap, easy available, and their mode of preparation is simple.

Heavy-metal tolerant bacterial strains isolated from industrial sites and scrap yards in Kashmir, India.

Heavy metal pollution has posed a severe danger to environmental stability due to its high toxicity and lack of biodegradability. The present study deals with the appraisement of tolerance shown by various bacteria in varied copper and iron concentrations. Among the 20 isolates, four isolates, GN2, SC5, SC8, and SC10, exhibiting more significant iron and copper tolerance, were selected and identified by 16 S ribosomal ribonucleic acid (rRNA) gene sequence analysis as Pantoea agglomerans strain GN2, Pantoea sp. strain SC5, Bacillus sp. strain SC8 and Priestia aryabhattaistrain SC10. The minimum inhibitory concentration of molecularly identified strains revealed that P. agglomerans strain GN2 showed tolerance to iron sulfate and copper sulfate upto 600 and 400 µg/mL, whereas Bacillus sp. SC8 (OQ202165) showed tolerance of 700 and 250 µg/mL were tolerant to iron sulfate and copper sulfate up to 700 and 150 µg/mL, respectively. Pantoea sp. strain SC5 showed significant tolerance to both heavy metals. The isolates were further studied for their ability to grow at varying temperatures and pH ranges. Most of the isolates showed optimal growth at 37°C and pH 7. However, Pantoea sp. SC5 was competent to have prominent growth at 45°C and pH 8.0. Microbial remediation, which is eco-friendly, has proven the most effective method for bioremediation of heavy metal-contaminated environments. Using heavy metal-resistant bacteria for microbial remediation of iron and copper-contaminated environments could be a viable and valuable strategy. These isolates could also be used to decontaminate heavy metal-polluted agricultural soils.

Unraveling the Variability of Essential Oil Composition in Different Accessions of Bunium persicum Collected from Different Temperate Micro-Climates.

The present investigation was performed to evaluate the variability of the essential oil composition present in the seed extract of Kala zeera (Bunium persicum Bioss.) obtained from different geographical zones of Northwestern-Himalayan using Gas Chromatography-Mass Spectrum (GC-MS). The results of the GC-MS analysis revealed significant differences in the essential oil content. Significant variability was observed in the chemical constituents of the essential oils mainly for p-cymene, D-limonene, Gamma-terpinene, Cumic aldehyde and 1, 4-p-menthadien-7-al. Among these compounds, the highest average percentage across the locations was observed for gamma-terpinene (32.08%) which was followed by cumic aldehyde (25.07%), and 1, 4-p-menthadien-7-al (15.45%). Principal component analysis (PCA) also grouped the 4 highly significant compounds i.e., p-Cymene, Gamma-Terpinene, Cumic aldehyde, and 1,4-p-Menthadien-7-al into same cluster which are mainly distributed in Shalimar Kalazeera-1, and Atholi Kishtwar zones. The highest value of gamma-terpinene was recorded in Atholi accession (40.66%). However, among climatic zones Zabarwan Srinagar and Shalimar Kalazeera-1 was found to have highly positive significant correlation (0.99). The cophenetic correlation coefficient (c) was found to be 0.8334 during hierarchical clustering for 12 essential oil compounds showing that our results are highly correlated. Network analysis also showed the overlapping pattern and similar interaction between the 12 compounds as shown by hierarchical clustering analysis. From the results, it could be concluded that existence of variability among the various bioactive compounds of B. persicum which are probably to be incorporated to the potential list of drugs and may serve as good genetic source for various modern breeding programs.

Deciphering the recent trends in pesticide bioremediation using genome editing and multi-omics approaches: a review.

Pesticide pollution in recent times has emerged as a grave environmental problem contaminating both aquatic and terrestrial ecosystems owing to their widespread use. Bioremediation using gene editing and system biology could be developed as an eco-friendly and proficient tool to remediate pesticide-contaminated sites due to its advantages and greater public acceptance over the physical and chemical methods. However, it is indispensable to understand the different aspects associated with microbial metabolism and their physiology for efficient pesticide remediation. Therefore, this review paper analyses the different gene editing tools and multi-omics methods in microbes to produce relevant evidence regarding genes, proteins and metabolites associated with pesticide remediation and the approaches to contend against pesticide-induced stress. We systematically discussed and analyzed the recent reports (2015-2022) on multi-omics methods for pesticide degradation to elucidate the mechanisms and the recent advances associated with the behaviour of microbes under diverse environmental conditions. This study envisages that CRISPR-Cas, ZFN and TALEN as gene editing tools utilizing Pseudomonas, Escherichia coli and Achromobacter sp. can be employed for remediation of chlorpyrifos, parathion-methyl, carbaryl, triphenyltin and triazophos by creating gRNA for expressing specific genes for the bioremediation. Similarly, systems biology accompanying multi-omics tactics revealed that microbial strains from Paenibacillus, Pseudomonas putida, Burkholderia cenocepacia, Rhodococcus sp. and Pencillium oxalicum are capable of degrading deltamethrin, p-nitrophenol, chlorimuron-ethyl and nicosulfuron. This review lends notable insights into the research gaps and provides potential solutions for pesticide remediation by using different microbe-assisted technologies. The inferences drawn from the current study will help researchers, ecologists, and decision-makers gain comprehensive knowledge of value and application of systems biology and gene editing in bioremediation assessments.

Cyanotoxins, biosynthetic gene clusters, and factors modulating cyanotoxin biosynthesis.

Cyanobacterial harmful algal blooms (CHABs) are a global environmental concern that encompasses public health issues, water availability, and water quality owing to the production of various secondary metabolites (SMs), including cyanotoxins in freshwater, brackish water, and marine ecosystems. The frequency, extent, magnitude, and duration of CHABs are increasing globally. Cyanobacterial species traits and changing environmental conditions, including anthropogenic pressure, eutrophication, and global climate change, together allow cyanobacteria to thrive. The cyanotoxins include a diverse range of low molecular weight compounds with varying biochemical properties and modes of action. With the application of modern molecular biology techniques, many important aspects of cyanobacteria are being elucidated, including aspects of their diversity, gene-environment interactions, and genes that express cyanotoxins. The toxicological, environmental, and economic impacts of CHABs strongly advocate the need for continuing, extensive efforts to monitor cyanobacterial growth and to understand the mechanisms regulating species composition and cyanotoxin biosynthesis. In this review, we critically examined the genomic organization of some cyanobacterial species that lead to the production of cyanotoxins and their characteristic properties discovered to date.

Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein.

Background and Objectives: Cyclooxygenase-2 (COX-2) is mostly linked to inflammation and has been validated as a molecular target for treating inflammatory diseases. The present study aimed to identify novel compounds that could inhibit COX-2, which is associated with various diseases including inflammation, and in such a scenario, plant-derived biomolecules have been considered as attractive candidates. Materials and Methods: In the present study, physiochemical properties and toxicity of natural compounds/drugs were determined by SWISSADME and ProTox-II. In the present study, the molecular docking binding features of saffron derivatives (crocetin, picrocrocin, quercetin, safranal, crocin, rutin, and dimethylcrocetin) against human COX-2 protein were assessed. Moreover, protein-protein interactions, topographic properties, gene enrichment analysis and molecular dynamics simulation were also determined. Results: The present study revealed that picrocrocin showed the highest binding affinity of -8.1 kcal/mol when docked against the COX-2 protein. PROCHECK analysis revealed that 90.3% of the protein residues were found in the most favored region. Compartmentalized Protein-Protein Interaction identified 90 interactions with an average interaction score of 0.62, and the highest localization score of 0.99 found in secretory pathways. The Computed Atlas of Surface Topography of Proteins was used to identify binding pockets and important residues that could serve as drug targets. Use of WEBnmα revealed protein dynamics by using normal mode analysis. Ligand and Receptor Dynamics used the Molecular Generalized Born Surface Area approach to determine the binding free energy of the protein. Gene enrichment analysis revealed that ovarian steroidogenesis, was the most significant enrichment pathway. Molecular dynamic simulations were executed for the best docked (COX-2-picrocrocin) complex, and the results displayed conformational alterations with more pronounced surface residue fluctuations in COX-2 with loss of the intra-protein hydrogen bonding network. The direct interaction of picrocrocin with various crucial amino-acid residues like GLN203, TYR385, HIS386 and 388, ASN382, and TRP387 causes modifications in these residues, which ultimately attenuates the activity of COX-2 protein. Conclusions: The present study revealed that picrocrocin was the most effective biomolecule and could be repurposed via computational approaches. However, various in vivo and in vitro observations are still needed.

Metabolic and Genetic Association of Vitamin D with Calcium Signaling and Insulin Resistance.

Various evidences have unveiled the significance of Vitamin D in diverse processes which include its action in prevention of immune dysfunction, cancer and cardiometabolic disorders. Studies have confirmed the function of VD in controlling the expression of approximately nine hundred genes including gene expression of insulin. VD insufficiency may be linked with the pathogenesis of diseases that are associated with insulin resistance (IR) including diabetes as well as obesity. Thus, VD lowers IR-related disorders such as inflammation and oxidative stress. This review provides an insight regarding the molecular mechanism manifesting, how insufficiency of VD may be connected with the IR and diabetes. It also discusses the effect of VD in maintaining the Ca2+ levels in beta cells of the pancreas and in the tissues that are responsive to insulin.