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B-cell lymphoma/leukemia gene-2 (Bcl-2) is the primary proto-oncogene that has been shown to work by preventing apoptosis/programmed cell death. Bcl-2 combines a variety of cell-generated signals associated to the survival and death of cells. In glioma, lung, and breast cancer, Bcl-2 over-expression has been linked to an increase in invasion and migration. Many treatment regimens that target Bcl2 have been established and approved, and thus increasing the survival rates of the patients. The primary goal of this research was to recognize new therapeutic compounds that target Bcl2 and assess Bcl2 expression pattern in BC patients. We used various bioinformatic tools as well as several in vitro assays to look out the expression and inhibition of Bcl2 in BC. Our study depicted that Bcl2 had a strong connection with tumour stroma, notably with suppressor cells originating from myeloid tissues. Moreover, in vitro and in silico research identified Paclitaxel as a promising natural substance that targets Bcl2. Overall, this work shows that Bcl2 overexpression accelerates the development of BC, and that targeting Bcl2 in combination with other drugs will dramatically improve BC patient's response to treatment and prevent the emergence of drug resistance., 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 The Author(s).)

Breast cancer is the primary factor contributing to female mortality worldwide. The incidence has overtaken lung cancer. It is the most difficult illness due to its heterogeneity and is made up of several subtypes, including Luminal A and B, basal-like, Her-2 overexpressed and TNBC. Amongst different breast carcinoma subtypes, TNBC is the most deadly breast cancer subtype. The hostile nature of TNBC is mainly attributed to its lack of three hormonal receptors and hence lack of targeted therapy. Furthermore, the current diagnostic options like radiotherapy, surgery and chemotherapy render unsuccessful due to recurrence, treatment side effects and drug resistance. The majority of anticancer drugs come from natural sources or is developed from them, making nature a significant source of many medicines. Marine-based constituents such as nucleotides, proteins, peptides, and amides are receiving a lot of interest in the field of cancer treatment due to their bioactive properties. The role of stypoldione in this study as a prospective treatment for breast carcinoma was examined, and we sought to comprehend the molecular means/pathways this chemical employs in breast carcinoma. The most promising possibility for an anti-cancer treatment is stypoldione, a marine chemical produced from the brown alga Stypopodium zonale . We investigated stypoldione's mode of action in breast cancer using the network pharmacology method, and we confirmed our research by using a number of computational tools, including UALCAN, cBioportal, TIMER, docking, and simulation. The findings revealed 92 common targets between the chemical and breast cancer target network. Additionally, we found that stypoldione targets a number of unregulated genes in breast cancer, including: ESR1, HSP90AA1, CXCL8, PTGS2, APP, MDM2, JAK2, KDR, LCK, GRM5, MAPK14, KIT, and several signaling pathways such as FOXO signaling pathway, VEGF pathway, calcium signaling pathway, MAPK/ERK pathway and Neuroactive ligand-receptor interaction. The examined medication demonstrated a strong affinity for the major targets, according to a docking analysis. The best hit compound produced a stable protein-ligand pair, as predicted by molecular dynamics simulations. Our results are supported by the fact that when in-vitro assays were done on melanoma using stypoldione compound it was found that its mechanisms of action involved the PI3K/mTOR/Akt and NF-kB pathways. This study was set out to inspect the possible value of stypoldione as a breast cancer cure and to get a deeper understanding of the molecular mechanisms by which this drug acts on breast cancer., 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 The Author(s).)

Interleukin 19 (IL-19) is a cytokine produced by monocytes and belongs to the family of IL-10. The IL-19 protein stimulates fibronectin (FN) expression and assembly, metastasis, and cell division in breast cancer (BC) cells. IL-19, which is connected to breast pathogenesis and has an autocrine action in BC cells, is a key predictor of prognosis for many tumour forms, including breast cancer. Augmented IL-19 expression has been related to poorer clinical outcomes for patients with BC and directly enhances proliferation and migration while also serving as a microenvironment for tumour formation. The main aim of our study was to examine the expression profile, functional role, and prognostic significance of interleukin-19 in BC pathogenesis and also to find out the molecular mechanism of IL-19 in BC. In this work, we used the various computational approach and tools, to evaluate the expression profile and prognostic implication of IL-19 in BC and discover the role of IL-19 in BC pathogenesis. IL-19 was shown to be highly upregulated in BC as compared to other interleukins. Also, its levels were highly overexpressed in liminal BC patients, mostly in 3rd stage groups under the age group of 21-40 years. IL-19 levels were increased in BC and elevated expression of IL-19 was examined to have worse overall survival (OS). The KEGG analysis and gene ontology of IL-19 depict that IL-19 is significantly augmented in cytokine activity and receptor-ligand activity and also in the JAK-STAT signaling pathway. Moreover, IL-19 showed a high correlation with IL20RA, as later is involved with the JAK-STAT signaling pathway. The in-vivo and in-vitro studies have also reflected that upregulation of IL-19 enhances tumor development and affects clinical outcomes in BC patients through several pathways including the JAK TAT signalling pathway. Overall, our study indicates that IL-19 increases tumour growth and that inhibiting it in addition to standard treatments will greatly improve BC patient's therapeutic responses., 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 The Author(s).)

Breast cancer is the leading cause of death among women worldwide. Despite the recent treatment options like surgery, chemotherapy etc. the lethality of breast cancer is alarming. Natural compounds are considered a better treatment option against breast carcinoma because of their lower side effects and specificity in targeting important proteins involved in the aberrant activation of pathways in breast cancer. A recently discovered compound called Juglanthraquinone C, which is found in the bark of the Juglans mandshurica Maxim (Juglandaceae) tree has shown promising cytotoxicity in hepatocellular carcinoma. However, not much data is available on the molecular mechanisms followed by this compound. Therefore, we aimed to investigate the molecular mechanism followed by Juglanthraquinone C against breast cancer. We used the network pharmacology technique to analyse the mechanism of action of Juglanthraquinone C in breast cancer and validated our study by applying various computational tools such as UALCAN, cBioportal, TIMER, docking and simulation. The results showed the compound and breast cancer target network shared 31 common targets . Moreover, we observed that Juglanthraquinone C targets multiple deregulated genes in breast cancer such as TP53, TGIF1, IGF1R, SMAD3, JUN, CDC42, HBEGF, FOS and signaling pathways such as PI3K-Akt pathway, TGF-β signaling pathway, MAPK pathway and HIPPO signaling pathway . A docking examination revealed that the investigated drug had a high affinity for the primary target TGIF1 protein. A stable protein-ligand combination was generated by the best hit molecule, according to molecular dynamics modeling. The main aim of this study was to examine Juglanthraquinone C's significance as a prospective breast cancer treatment and to better understand the molecular mechanism this substance uses in breast cancer since there is a need to discover new therapeutics to decrease the load on current therapeutics which also are currently ineffective due to several side effects and development of drug resistance., 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 The Author(s).)

Human infectious diseases caused by various microbial pathogens, in general, impact a large population of individuals every year. These microbial diseases that spread quickly remain to be a big issue in various health-related domains and to withstand the negative drug impacts, the antimicrobial-resistant pathogenic microbial organisms (pathogenic bacteria and pathogenic fungi) have developed a variety of resistance processes against many antimicrobial drug classes. During the COVID-19 outbreak, there seems to be an upsurge in drug and multidrug resistant-associated pathogenic microbial species. The preponderance of existing antimicrobials isn't completely effective, which limits their application in clinical settings. Several naturally occurring chemicals produced from bacteria, plants, animals, marine species, and other sources are now being studied for antimicrobial characteristics. These natural antimicrobial compounds extracted from different sources have been demonstrated to be effective against a variety of diseases, although plants remain the most abundant source. These compounds have shown promise in reducing the microbial diseases linked to the development of drug tolerance and resistance. This paper offers a detailed review of some of the most vital and promising natural compounds and their derivatives against various human infectious microbial organisms. The inhibitory action of different natural antimicrobial compounds, and their possible mechanism of antimicrobial action against a range of pathogenic fungal and bacterial organisms, is provided. The review will be useful in refining current antimicrobial (antifungal and antibacterial) medicines as well as establishing new treatment strategies to tackle the rising number of human bacterial and fungal-associated infections., 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., (© 2022 The Authors.)

There is interrelationship of the environmental conditions and fish health. Decrease or increase of pollution in aquatic ecosystem have direct impact on presence or absence of parasites. Fish living under optimum environmental, well-nourished conditions are more resistant to diseases than fish weakened by malnutrition caused by parasite infestation or due to deterioration of environmental conditions because ofpollution. Fish encounters common parasites in wild and in culture systems. Parasites attach to the host through suckers and hooks and make their way inside the host through different means, which include skin, through mouth along with food, by means of gills. The hosts were collected during Jan 2019 to Jan 2020 from river Veshaw. During this study it was observed that presence of parasites causes some changes in fish which can serve as indicators of deterioration in aquatic habitat. Clinical signs were noticed in fish hosts collected from sites which received waste due to anthropogenic activities. Parasitic anomalies in the host collected from polluted site was observed to include body deformaties, gastric distention, lesions in gut, increased mucus production, damage in gill filaments etc ., 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., (© 2022 The Author(s).)

De novo reference intervals (RIs) for a total of thirty two hematological and serum biochemical attributes were established for rainbow trout ( Oncorhynchus mykiss ) cultured in Himalayan aquaculture system. For this purpose, long term assessment of hemato-biochemical parameters was carried over a period of one year from March 2019 to February 2020 and a total of 444 blood samples were analysed. Blood examination results were recorded systematically and reference intervals were established, notably for erythrocyte parameters: hematocrit (Hct) 29-40%, hemoglobin 8.32-12.28 g/dL, red blood cell (RBC) count 1.01-2.04 (×10 6 /mm3); leukocyte parameters (x 10 3 /mm3): total leukocytes 31.32-90.60, neutrophils 4.21-18.85, total lymphocytes 20.55-63.63, small lymphocytes 14.86-46.50, large lymphocytes 6.35-22.34 and monocytes 1.22-7.56; thrombocyte count 23.00-68.00 (×10 6 /mm3). RIs were also established for red blood cell indices, vital serum constituents involved in carbohydrate, protein, lipid and nitrogen metabolism including the less known, diagnostically important, serum enzymes and electrolyte concentrations. Principal component analysis revealed that certain serum components were more efficient at distinguishing between the life stages (juvenile, adult) of fish by explaining about 92.7% of variation in the whole dataset compared to the principal hematological components which explained only about 80% of the variation. Significant ( P  < 0.05) differences were noted for RBC count, total leukocyte count (TLC), total protein, total cholesterol and uric acid with respect to the sex of fish. Moreover, clearly differentiable morphometric and morphological attributes were also noticed among erythrocytes, leukocytes (lymphocytes, neutrophils and monocytes) and thrombocytes. To our knowledge, the present study is the first of its kind that elucidates blood chemistry of cultured rainbow trout, O. mykiss in accordance to the guidelines framed by the American society of veterinary clinical pathologists (ASVCP). RIs reported here can help monitor the fish health status by improving the use of non-lethal diagnostics in piscine medicine., 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., (© 2022 Published by Elsevier B.V. on behalf of King Saud University.)

Postharvest losses of cut flowers is one of the considerable challenges restricting their efficient marketability. Consequently, such challenges have triggered a constant hunt for developing compatible postharvest treatments to mitigate postharvest losses. Interestingly, recent studies entrench extensive role of salicylic acid (SA) in mitigating postharvest losses in various flower systems. The current investigation focusses on role of SA in augmenting physiological and biochemical responses to mitigate postharvest senescence in cut spikes of Consolida ajacis . The cut spikes of C. ajacis were supplemented with various SA treatments viz, 2 mM, 4 mM, 6 mM. The effects of these treatments were evaluated against control set of spikes placed in distilled water. Our study indicates considerable increment in postharvest longevity of cut spikes, besides an increase in solution uptake, sugar and protein content of tepal tissues.SA augmented antioxidant system via upsurge in phenolic content and antioxidant enzymes viz, superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) to forfend reactive oxygen species (ROS) related oxidative damage. SA profoundly reduced lipoxygenase (LOX) activity to preserve the membrane integrity and thus prevented seepage of solutes from tepal tissues. These results authenticate SA particularly 4 mM concentration as effective postharvest treatment to preserve the postharvest quality of C. ajacis cut spikes., 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., (© 2021 The Author(s).)

Background: Tumor necrosis factor interacting protein (TRAIP/TRIP) is an important cell-signaling molecule that prevents the TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation via direct interaction with TRAF 2 protein. TRAIP is a crucial downstream signaling molecule, implicated in several signaling pathways. Due to these multifunctional effects, TRAIP is more related to cellular mitosis, chromosome segregation, and DNA damage response. Tumor necrosis factor interacting protein is a downstream signaling molecule that contains a RING domain with E3 ubiquitin ligase activity at the N terminal side followed by coiled-coil and C terminal leucine zipper domain. Human TRAIP is constituted of 469 amino acids with 76% sequence similarity with the mouse TRAIP protein. Although, the main inhibitory function of TRAIP has been known for decades, however, in vitro interaction of TRAIPCC domain with RAP80 Zinc finger motif has not been reported yet. Besides, RAP80, the binding partner of TRAIPCC protein has been implicated in DNA damage response., Results: Our in vitro study shows that the TRAIP CC (64-166) associates with the RAP80 zinc finger of corresponding amino acid 490-584. However, TRAIP CCLZ (66-260) and TRAIP RINGCC (1 = 157) failed to interact with the RAP80 zinc finger of corresponding amino acid 490-584. The current study reinforces TRAIP CC (64-166) and RAP80 zinc finger of corresponding amino acid 490-584 associates to form a complex. Moreover, SDS PAGE arbitrated the homogeneity of RAP80 Zinc finger and TRAIP CC of corresponding amino acid 490-584 and 64-166, respectively., Conclusion: In vitro , a specific interaction was observed between the TRAIP CC (64-166) and the RAP80 zinc finger of the corresponding amino acid 490-584 and a specific binding area of the RAP80 zinc finger motif were investigated. The TRAIPCC region is required for the complex to bind to the RAP80-Zn finger motif. This strategy may be necessary for the RAP80 zinc finger activity to the TRAIP CC protein., 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., (© 2021 The Author(s).)

Food and nutritional security continue to be the issues of concern in developing countries like ours. Exploring the reservoir of high potential unexplored genetic resources could address the world's food and nutritional insecurity. The availability of diverse data and the population structure of any crop germplasm is a valuable genetic resource for discovering genes that can help achieve food and nutritional stability. We used seven ISSR and seven SSR markers to investigate diversity among 63 buckwheat genotypes, including landraces from India's northwestern Himalayas. Various parameters such as percent polymorphism, PIC, resolving power, and marker index was used to evaluate the inequitable efficacy of these markers. We foundthat both marker systems are effective in detecting polymorphism in buckwheat germplasm. Seven ISSRs produced 55 polymorphic bands, while seven SSRs produced 32bands. When compared to ISSRs, SSRs had a greater average PIC value (0.43) than that of (0.36). ISSRs, on the other hand, had a resolving power of (4.38) compared to (1.42) for SSRs. The hierarchical cluster analysis dendrogram divided genotypes into three major clusters. We found that both marker systems were equally accurate in grouping buckwheat genotypes according to their geographical origins. Using 7 ISSR and 7 SSR markers, the model-based STRUCTURE analysis established a population with two sub-populations that correspond to species-based groupings. Within the population, there was a high level of genetic diversity. These results have consequences for both buckwheat breeding and conservation efforts., 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., (© 2021 The Authors.)

The overproduction of reactive oxygen species (ROS) causes oxidative stress, such as Hydrogen peroxide (H 2 O 2 ). Acute oxidative stress is one of the main reasons for cell death. In this study, the antioxidant properties of vanillic acid- a polyphenolic compound was evaluated. Therefore, this study aims to check the effectiveness of vanillic acid in H 2 O 2 -induced oxidative stress in D. Mel-2 cell line. The efficacy was determined by biochemical tests to check the ROS production. The cytotoxicity of H 2 O 2 and vanillic acid was checked by MTT assay. The DNA fragmentation was visualized by gel electrophoresis. Protein biomarkers of oxidative stress were analyzed by western blotting. The results depict a promising antioxidant effect of vanillic acid. The IC 50 value of vanillic acid and H 2 O 2 was found 250 μg/ml and 125 μg/ml, respectively. The catalase activity, SOF, GPx, and PC was seen less in H 2 O 2 treated group compared with the control and vanillic acid treated group. However, the TBRAS activity was hight in H 2 O 2 treated group. The effect of H 2 O 2 on DNA fragmentation was high as compared with vanillic acid-treated cells. The protein expression of Hsp70, IL-6 and iNOS was seen significant in a vanillic acid-treated group as compared with H 2 O 2 treated group. These results reinforce that at low concentration, vanillic acid could be used as an antioxidant agent in the food and pharmaceutical industries., 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., (© 2020 The Author(s).)

The formation of inflammasome complexes contributes inactivation of inflammatory caspases viz caspase 1, which is generally considered essential for the innate response. Three proteins constituted this inflammasome complex, such as Nod-like receptors (NLRP or AIM2), ASC possessing caspase-recruiting domain, and caspase-1. The ASC proteins comprise two domains, the N-terminal PYD domain responsible for the interaction of various proteins, including PYD only protein 3 (POP3), and the CARD domain for association with other proteins. The PYRIN Domain-Only Protein POP3 negatively regulates responses to DNA virus infection by preventing the ALR inflammasome formation. POP3 directly interacts with ASC, therefore inhibiting ASC recruitment to AIM2-like receptors (ALRs). In the current study, we designed various constructs of the PYRIN Domain-Only Protein 3 (POP3) and ASC PYD domain to find the best-overexpressed construct for biochemical characterization as well as our complex studies. We cloned, purified, and characterized the PYD domain of pyrin only protein 3 and ASC PYD domain under physiological conditions. Our in vitro study clearly shows that the ASC PYD domain of corresponding amino acid 1-96 aa with ease self-oligomerization in physiological buffer conditions, and complex formation of POP3 PYD (1-83 aa) was inhibited by ASC PYD domain. Besides, we purified the PYD of POP3 protein in low and high salt conditions and different pH values for their biochemical characterization. Our results showed that POP3 formed a dimer under normal physiological conditions and was stable under normal buffer conditions; however, the purification in extremely low pH (pH5.0) conditions shows unstable behavior, the high salt conditions (500 mM NaCl) influence the protein aggregation. SDS PAGE arbitrated the homogeneity of the PYD domain of pyrin only protein 3 and ASC PYD domain of corresponding amino acids 1-83 and 1-96, respectively. Furthermore, our native PAGE shows the PYD domain of pyrin; only protein 3 did not form a complex with ASC PYD domain because of oligomerization mediated by the PYD domain., Competing Interests: All authors declare that there are no conflicts of interest., (© 2021 The Author(s).)

Candidal vulvovaginitis (CVV), is the second most leading vaginal infection (global prevalence > 75%), caused due to excessive growth of Candida spp. , predominantly Candida albicans (>95% cases). The current treatment regimens for CVV are marred with the challenges of fungal resistance & infection recurrence, subsequently leading to the compromised therapeutic efficacy of anti-fungal drugs, prolonged treatment and low patient compliance. The core of the present research was the fabrication & investigation of 2 T-SLN (solid lipid nanoparticles) gel carrying luliconazole for the amelioration of CVV. '2T' symbolizes transvaginal & thermosensitive attributes of the present formulation. SLNs were prepared by a modified melt emulsification-ultra sonication method using a combination of solid lipids (Gelucire 50/13 & Precirol ATO 5), surfactant (Tween 80) and co-surfactant (Kolliphor). Formulation by design (FbD) approach was adopted to obtain appropriately screened and tailored SLNs. The optimized SLNs yielded a particle size, polydispersity index & entrapment efficiency of 62.18 nm, 0.263 & 81.5% respectively. To formulate the 2 T-gel, the final SLNs were loaded into Carbopol 971P-NF and Triethanolamine based gel. The 2 T-SLN gel was found to be easily spreadable and homogenous with mean extrudability (15 ± 0.4 g/cm 2 ), viscosity (696.42 ± 2.34 Pa·s) and %drug content (93.24 ± 0.73%) values.. The pH of the prepared 2 T-SLN gel (4.5 ± 0.5) was in concordance with the vaginal pH (normal conditions). For in-vitro characterization of an optimized 2 T-SLN gel the release kinetics & anticandidal activity were assessed which offers a %cumulative drug release of 62 ± 0.5% in 72 h and 37.3 ± 1.5 mm zone of inhibition in 48 h. The visual appearance & dimensions were determined using fluorescent microscopy (spherical shape) & transmission electron microscopy (90-120 nm) respectively. The optimized 2 T-SLN gel showcases a skin-friendly profile with no significant signs of erythema and oedema and was found to be stable at room temperature for 2 months without any visual non-uniformity/cracking/breaking. In conclusion, the current research serves a new therapeutic perspective in assessing the activity of luliconazole for vaginal drug delivery using a 2 T-SLN gel system., (© 2020 The Authors.)

The purpose of this study was to evaluate etiology and pregnancy outcome of recurrent miscarriage women. The enrolled patients (280) were evaluated for Triiodothyronine, Thyroxine, Thyroid stimulating hormone, prolactin, chromosomal analysis, Haemoglobin A1C, blood sugar, Magnetic resonance imaging, 3D-ultrasound, auto-antibodies profile (antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies, anti-thyroid antibodies and β2 glycoprotein1), torch profile (Toxoplasmo gondii, rubella, cytomegalo virus and herpes simplex virus), blood vitamin D3 levels, psychological factors, Body mass index and thrombotic factors (protein S and C deficiency, Prothrombin G20210A mutation, anti-thrombin III, Factor V Leiden and Methylenetetrahydrofolate reductase mutation), uterosalpingography (hysteronsalpingography) and hysteroscopy. The therapeutic regimens either singly or combined were employed for the treatment of recurrent miscarriage patients on the basis of etiology (single or multiple) and include intravenous immunoglobulin, low molecular weight heparin, low dose aspirin, levothyroxine, progesterone, folic acid, human chorionic gonadotrophin, vitamin D3, psychotherapy, genetic counselling. However, patients with idiopathic recurrent miscarriage were treated with progesterone supplementation, anticoagulation and/or immune modulatory agents. The incidence of primary recurrent miscarriage was highest and most of the women experienced recurrent miscarriage during first trimester. Endocrinological disorders (39%) were found as the major pathological factor for recurrent miscarriage. Other factors include uterine abnormalities (5.7%), vitamin D3 deficiency (3.5%), psychological factors (3.2%) infection (3.6%), autoimmune abnormalities (1.8%) and protein S deficiency (1.8%). However, 40% cases were idiopathic. The overall live birth rate achieved after the management of recurrent miscarriage patients was 75.7%. Enocrinopathy was the major cause of recurrent miscarriage. The overall live birth rate achieved was 75.7% with highest pregnancy outcome in secondary recurrent miscarriage patients after the management., (© 2020 The Authors.)

During the last few decades, human-driven activities have led to indiscriminate habitat destruction and exploitation of many plant species in Kashmir Himalaya. As a result, many species have become threatened and are struggling for survival. Of particular concern are the endemic and critically endangered species which have the highest risk of the extinction, hence warranting immediate conservation actions. Therefore the current study was carried out to understand the distribution, ecology and conservation implications of the four critically endangered endemic plants of Kashmir Himalaya. Habitat distribution modelling showed that the suitable potential areas for the species occurred from subalpine to alpine meadowlands with an elevational range of 1500-4600 m asl. The output of the MaxEnt model and field surveys have revealed that their highest potential distribution is in Panchari, Khrew, Ramnagar, Pahalgam, Gurez, Sonamarg, Gulmarg and Kishtwar forest ranges. Based on the field explorations and herbarium records, Saussurea costus (Falc.) Lipsch have 27 distribution areas, Gentiana kurroo Royle 18, Lilium polyphyllum D. Don 12 and Aconitum chasmanthum Stapf have 15. Precipitation of the driest month and annual mean temperature played an important role in the distribution of the studied species. The species started their lifecycle with the onset of the spring season, flowered in summer, fruit in autumn and senesce in the winter season. Under natural conditions, the number of days required for germination ranged from 180 to 210 where cold stratification played a pivotal role. Since last few decades, the populations of these species have been shrinking in their natural habitats due to over-exploitation for medicinal purposes and habitat destruction through amplified humanoid interferences like the expansion of agricultural land, road building, grazing and urbanization. Thus there is an urgent need to come up with positive strategies to save whatever is left and plan long term rescue measures not only to protect these species from extinction but also to reintroduce them along with framing the plans to supply sustained raw materials for medicine., Competing Interests: None., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

Toxic metal contamination in soils due industrialization is nowadays a concern to the scientists worldwide. The current study deals with the evaluation of response and tolerance by isolated metallophilic bacteria in different lead concentrations (100 ppm to 1000 ppm). By taking optical densities of the isolates, the minimum inhibitory concentration (MIC) of Pb 2+ were determined.16S rRNA and MALDI-TOF MS were used for the identification of the bacteria. Total of 37 isolates were observed, among them 04 ( Staphylococcus equorum, Staphylococcus warneri , Bacillus safensis and Bacillus thuringiensis ), isolated were detected having efficacy of Pb 2+ tolerance and sequestration at varying MIC. Furthermore, B. thuringiensis was observed to have highest (900 ppm) tolerance for lead and lowest (500 ppm) for Staphylococcus warneri. Moreover, the highest (65.3%) sequestration potential has been observed for B. thuringiensis and least (52.8%) for S. warneri. The tolerance and sequestration potential properties of these isolated species can be utilised to exterminate heavy metals and reduce their toxicity from the contaminated environment., 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., (© 2020 The Authors.)

The TRAIP interacting protein is known as a negative regulator of TNF-induced-nuclear factor, kappa-light-chain-enhancer of activated B cell (NF-κB) by direct interaction with the adaptor protein TRAF2, which inhibits the function of TRAF2 via the RINGCC domain protein. The TRAIP protein is composed of 469 amino acids with an N-terminal RING motif that is followed by a coiled coil (CC) and leucine zipper domain. TRAIP proteins are critical in programmed cell death, cell proliferation and differentiation, and embryonic development. The critical functions of TRAIP together with the molecular inhibitory mechanism effect of TRAIP have been reported by two different studies and have opened up new research into the field of TRAF biology. In this study, we designed different constructs of the Leucine zipper domain to find the over -expressed construct for further studies. We successfully cloned the C-terminal TRAIP containing the leucine zipper domain. In addition, we have over-expressed and purified the TRAIP LZ for their biochemical characterization., 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., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

Saffron plant ( Crocus sativus L.) is being used as a source of saffron spice and medicine to cure or prevent different types of diseases including cancers. We report the isolation, characterization of bioactive small molecule ([crocetin (β-d-glucosyl) ester] from the leaf biowastes of saffron plant of Kashmir, India. MTTC assay and Bio-autography aided approach were used to assess anti-oxidant activity and anti-cancer properties of crocin (s) against DPPH free radical and breast cancer cell line respectively. Crocetin beta-d-glucosyl ester restrained proliferation of human breast adeno-carcinoma cell model (MCF-7) without significantly affecting normal cell line (L-6). Further studies involving molecular mechanics generalized born surface area and molecular docking showed that crocetin beta-d-glucosyl ester exhibits strong affinity for estrogen receptor alpha and histone deacetylase 2 (crucial receptors involved in breast cancer signalling) as evidenced by the negative docking score and binding free energy (BFE) values. Therefore, crocetin beta-d-glucosyl ester from Crocus sativus biowastes showed antiproliferative effect possibly by inhibiting estrogen receptor alpha and HDAC2 mediated signalling cascade., (© 2020 The Author(s).)

Broadly speaking proteomic studies are one of the various techniques of utmost importance for understanding complex biological processes that occur under inductive conditions and revealing the multidimensional aspects of Crocus sativus in biological systems. In order to get an insight into the molecular changes and to characterize the variations in protein expression of C. sativus , a detailed proteomic analysis on one-dimensional gel electrophoresis is one of the basic steps to accomplish. We have compared total protein profiles of C. sativus extracted by three different recipes and analyzed on 10% sodium dodecyl sulfate polyacrylamide gels. Gels were subjected to densitometric analysis for further characterization. Among three different protocols NP-40 extraction buffer recipe resulted in the extraction of proteins most efficiently with minimum background and streaking. There was maximum solubilization of proteins with high efficiency. Such a profile can be used for high precision analysis of differential protein expression. This work is an attempt to assist researchers in effective extraction of proteins from C. sativus . As a researcher faces a perplexing array of choices as where to start we describe a method based on our collective analysis of the different protein protocols. This paper presents a method that could be applied at the outset of any proteomic study.

How changes in biodiversity alter the transmission of infectious diseases is presently under debate. Epidemiologists and ecologists have put a lot of effort to understand the mechanism behind biodiversity-disease relationship. Two important mechanisms, i.e. dilution and amplification theories have in some manner made it clear that biodiversity and disease outcome have an intimate relationship. The dilution effect theory seems to answer some overarching questions, but paucity of information about many disease systems is a real obstacle for its acceptance. Also, there is hardly any agreement on host population threshold and critical community size vis-à-vis wild life diseases. We suggest a multidimensional approach whereby the same disease system needs to be studied in different ecological zones and then the effect of biodiversity on disease outcome needs to be ascertained. Nonetheless, caution is to be taken while jumping to any conclusion as biodiversity-disease relationship is a multifactorial process.

In this study our objective was to evaluate the antioxidant and antimicrobial activity of methanolic extracts of leaves and roots of Gentiana kurroo. The antioxidant activities of the extracts were examined using different biochemical assays namely diphenylpicrylhydrazyl (DPPH), nitroblue tetrazolium (NBT) and ferric reducing power (FRAP). In all the assays, root extract exhibited stronger antioxidant activity than that of leaves. The antibacterial activity of the extracts was also evaluated and MIC values were calculated by broth dilution method. Although, the extracts prevented the growth of both Gram positive and Gram negative bacteria, the MIC values of methanolic extract of the leaves were higher than those of the root extract. The antibacterial and antioxidant activity of the extracts was found to be positively associated with the total phenolic and flavonoid content of the extracts.