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Gastric cancer (GC)-diabetes co-morbidity is nowadays growing into a rising concern. However, no separate treatment procedures have been outlined for such patients. Phytochemicals and their derivatives can therefore be used as therapeutics as they have greater effectiveness, reduced toxicity, and a reduced likelihood of developing multi-drug resistance in cancer treatments. The present study intended to assess the therapeutic efficacy of Shatavarin-IV - a major steroidal saponin from the roots of Asparagus racemosus, in human gastric adenocarcinoma cell line under hyperglycemic conditions and explore its mechanism of action in controlling GC progression. For the present study, AGS cells were incubated in high glucose-containing media and the effects of Shatavarin-IV therein have been evaluated. Cell proliferation, confocal microscopic imaging, flow-cytometric analysis for cell cycle and apoptosis, immunoblotting, zymography, reverse zymography, wound-healing, colony formation, and invasion assays were performed. Shatavarin-IV has a prominent effect on AGS cell proliferation; with IC50 of 2.463 µ M under hyperglycemic conditions. Shatavarin-IV induces cell cycle arrest at the G0/G1 phase, thereby preventing hyperglycemia-induced excessive cell proliferation that later on leads to apoptotic cell death at 36 h of incubation. Shatavarin-IV further inhibits the migratory and invasive potential of AGS cells by altering the expression patterns of different EMT markers. It also inhibits MMP-9 while promoting TIMP-1 activity and expression; thereby regulating ECM turnover. This is the first report demonstrating the therapeutic efficacy of Shatavarin-IV against AGS cells grown in hyperglycemic conditions, implicating new insights into the treatment paradigm of patients with GC-diabetes co-morbidity., 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. Published by Elsevier Inc.)

Gastric cancer and diabetes are two complex and interrelated diseases having significant impact on global health. Hyperglycemic condition notably exacerbates cancer by promoting inflammation, angiogenesis, and metastasis. Elevated glucose levels can also upregulate the expression of specific matrix metalloproteinases (MMPs), especially MMP-9, which is associated with cancer cell migration and invasion. However, the molecular mechanism behind such upregulation remains unexplored. In the present study, we have identified the mechanism for hyperglycemia-induced transcriptional activation of MMP-9, in gastric adenocarcinoma (AGS) cells. Using various tools like luciferase-reporter assays with promoter deletion constructs, siRNAs, pharmacological inhibitors, and nuclear translocation experiments, we have identified that the transcriptional activation of MMP-9 under hyperglycemic conditions is predominantly governed by the MAPK pathway, via formation of the AP-1 heterodimer. The p65 NF-κB signaling pathway, although activated, plays no significant role in regulating hyperglycemia-induced MMP-9 expression. Chromatin immunoprecipitation studies indicate that the distal AP-1 binding site is responsible for hyperglycemia-induced MMP-9 transcription; whereas the proximal one accounts for both hyperglycemia-induced and basal MMP-9 transcription. Therefore, binding of AP-1 at both the proximal and distal binding sites on the MMP-9 promoter region is required for hyperglycemia-induced MMP-9 expression. Overall, our study unveils a novel mechanism of MMP-9 transcription under hyperglycemic conditions and also suggests that inhibiting the binding of the AP-1 heterodimer with its distal binding site can potentially reduce the complications developed during gastric cancer-hyperglycemia co-morbidity. A drug designed specifically to inhibit this interaction may prevent hyperglycemia-induced tumor aggressiveness to a considerable extent by impeding MMP-9 transcription., 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 Elsevier Inc. All rights reserved.)

Cancer cells utilize glucose as their primary energy source. The aggressive nature of cancer cells is therefore enhanced in hyperglycemic conditions. This study has been adopted to investigate the therapeutic potential of melatonin against such aggressive proliferation of AGS cells-a human gastric cancer cell line, under hyperglycemic conditions. AGS cells were incubated with high glucose-containing media, and the effects of melatonin have been evaluated, therein. Cell proliferation, ROS generation, flow-cytometric analysis for cell cycle and apoptosis, wound healing, immunoblotting, zymography, reverse zymography assays, in-silico analysis, and kinase activity assays were performed to evaluate the effects of melatonin. We observed that melatonin inhibited the hyperglycemia-induced cell proliferation in a dose-dependent manner. It further altered the expression and activity of MMP-9 and TIMP-1. Moreover, melatonin inhibited AGS cell proliferation by arresting AGS cells in the G 0 /G 1 phase after binding in the ATP binding site of CDK-2, thereby inhibiting its kinase activity. In association, a significant decrease in the expression of cyclin D1, cyclin E, CDK-4, and CDK-2 were observed. In conclusion, these findings suggest that melatonin has anti-gastric cancer potential. Melatonin could therefore be included in future drug designs for gastric cancer-hyperglycemia co-morbidity treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Enveloped viruses infect host cells via protein-mediated membrane fusion. However, insights into the microscopic rearrangement induced by the viral proteins and peptides have not yet emerged. Here, we report a new methodology to extract viral fusion peptide (FP)-mediated biomembrane dynamical nanodomain fusion parameter, λ, based on stimulated emission depletion microscopy coupled with fluorescence correlation spectroscopy. We also define another dynamical parameter membrane gradient, defined in terms of the ratio of average lipid diffusion coefficients across dynamic crossover length scales, ξ. Significantly, we observe that λ as well as these mobility gradients are larger in the stiffer liquid-ordered (L o ) phase compared to the liquid-disordered phase and are more effective at the smaller nanodomain interfaces, which are only present in the L o phase. The results could possibly help to resolve a long-standing puzzle about the enhanced fusogenicity of FP in the L o phase. Results obtained from the diffusion results have been correlated with the human immunodeficiency virus gp41 FP-induced membrane fusion.

Background: Cavendish (AAA) banana plant (Musa spp.) worldwide cultivated crop harbors many endophytic bacteria. Endophytic bacteria are those that live inside plant tissues without producing any visible symptoms of infection., Results: Endophytic bacterium (MRH 11), isolated from root tissue of Musa spp.was identified as Achromobacter xylosoxidans (ON955872) which showed positive effects in IAA production, phosphate solubilization, catalase production. A. xylosoxidans also showed in vitro antagonism against Curvularia lunata causing leaf spot disease of Cavendish (AAA) banana (G-9 variety). The GC-MS analysis of culture filtrate of A. xylosoxidans (ON955872) confirmed this finding. GC-MS analysis was carried by using two solvent etheyl acetate and chloroform and it showed several antifungal compounds. The identification of these bioactive secondary metabolites compounds was based on the peak area, retention time, molecular weight, molecular formula and antimicrobial actions. GC-MS analysis result revealed the presence of major components including Cyclododecane, 1-Octanol, Cetene, Diethyl phthalate. In vivo test to banana plants was carried out in separate field as well as in potted conditions. Appearance of leaf spots after foliar spray of spore of pathogen and reduction in leaf spots after application of bacterial suspension was found., Conclusion: The present study has highlighted the role of endophytic bacterium as antagonist to the pathogen Curvularia lunata., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Indomethacin, a known nonsteroidal anti-inflammatory drug (NSAID) induces gastric inflammation, causing degradation of the extracellular matrix by specific matrix metalloproteinases (MMPs). We investigated the antiulcer efficacy of 3-indolyl furanoids ( 3g and 3c , i.e., methoxy substitution at 4- and 5-positions of the indole ring, respectively), derived from indomethacin. Interestingly, 3g protected against indomethacin-induced gastropathy in vivo by inhibiting MMP-9. Our work established a chemical modification strategy for the development of safer NSAIDs. Moreover, in vitro and in silico studies confirmed that 3g inhibited MMP-9 activity with an IC 50 value of 50 μM by binding to the catalytic cleft of MMP-9, leading to ulcer prevention. Pharmacokinetics was presented as the mean concentration-time profile in the rat plasma, and the extraction efficiency was greater than 70%, showing a C max of 104.48 μg/mL after 6.0 h ( t max ) treatment with half-life and area under the curve being 7.0 h and 1273.8 h μg/mL, respectively, indicating the higher antiulcer potency of 3g .

In this paper, a photonic crystal (PhC) based 1×2 demultiplexer is designed to work efficiently at 1550 n m , which is the operating wavelength of optical communication. In designing a 1×2 demultiplexer, the PhC structure employs Y-shaped square-lattice silicon rods with air as its basis in accordance with the principle of beam interference. This study presents a 15×15 rod-based PhC optimized structure with air as its background. Several distinct phase studies are carried out making use of a wide variety of lattice constant and refractive index values of PhCs. The design achieves enhanced performance in accordance with parameters such as having higher contrast ratio of 15.64 dB, high transmission efficiency of 77.92%, fast response time of 15.03 fs, and low insertion loss of 1.08 dB with optimal values for refractive index (RI), silicon rod radius, and lattice constant. The results of the simulation that used the finite-difference-time-domain technique illustrate the good performance of this structure, which exhibits a higher contrast ratio and bit rate, average transmitted power, and fewer power losses.

Rotenone has widespread beneficial effects in agriculture, fisheries and animal husbandries; however prolonged exposure causes a detrimental effect on the health of personnel working in such industries. Rotenone during its extraction, formulation or usage may cross the blood brain barrier leading to neurodegeneration and the development of Parkinson's disease like symptoms. It is a known inhibitor of the mitochondrial ETC complex I and responsible for impairing the OXPHOS system. Our study showed that rotenone exposure results in an increased production of ROS and decreased ATP level along with a conspicuous loss of mitochondrial membrane potential in N2A cells. The transcription and expression pattern of cofilin, a key component of actin cytoskeleton, was also altered after rotenone exposure; leading to the actin cytoskeleton degradation. We further observed an increased expression, as well as activity of matrix metalloproteinase9 (MMP9) in rotenone exposed N2A cells; suggesting the involvement of inflammation upon rotenone exposure. Simultaneously, an opposite pattern was noticed for the tissue inhibitors of metalloproteinases-1 (TIMP-1) protein, which is a known modulator of MMP9 activity. Additionally, the localization of MMP9 along with alpha-synuclein, UCHL1 and cofilin suggested their close proximity and cross interaction upon rotenone treatment. Furthermore, we observed significant increase in the level of TNF-α upon rotenone exposure along with the phosphorylation of RIPK1, RIPK3 and MLKL that has been identified as the necroptosis markers leading to programmed necroptotic death., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work. We confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). She is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Universal gates (NAND and NOR) are used for any electronic circuit that is affordable and straightforward to build all logic gates (LoG). In this work, the T-shaped 2D photonic crystal (PhC) is exploited to design a three-input universal LoG premised on the beam-interference principle. The design criteria of pitch ( a ), rod radius ( r ), and refractive index ( n ) are employed to obtain a high impact output. The methodologies of plane wave expansion and finite-difference time-domain are employed for examining the framework of universal LoG at 1550 nm wavelengths ( λ ). The suggested universal LoG design has a compact size of 8.4µ m ×4.8µ m . Additionally, the structure yields a high contrast ratio (CR) of 20.37 dB for the NAND LoG and 28.45 dB for the NOR LoG, and maximum transmission efficiency of 50.6% and 70% for the NAND and NOR gates; correspondingly, the best and worst three-input NAND gate response times are 19.5 ps and 21.4 ps. Similarly, the response time of the three-input NOR gate is 26 ps. The proposed universal gate's primary goal is to offer a high CR and a compact structure while being compatible with any other logic gate.

The main effectors in the innate immune system of Bombyx mori L. are antimicrobial peptides (AMPs). Here, we infected B. mori with varied inoculum sizes of Pseudomonas aeruginosa ATCC 25668 cells to investigate changes in morpho-anatomical responses, physiological processes and AMP production. Ultraviolet-visible spectra revealed a sharp change in λ max from 278 to 285 nm (bathochromic shift) in the hemolymph of infected B. mori incubated for 24 h. Further, Fourier Transform InfraRed studies on the hemolymph extracted from the infected B. mori showed a peak at 1550 cm -1 , indicating the presence of α-helical peptides. The peptide fraction was obtained through methanol, acetic acid and water mixture (90:1:9) extraction, followed by peptide purification using Reverse Phase High Performance Liquid Chromatography. The fraction exhibiting antibacterial properties was collected and characterized by Matrix-Assisted Laser Desorption/Ionization-Time of Flight. A linear α-helical peptide with flexible termini (LLKELWTKMKGAGKAVLGKIKGLL) was found, corresponding to a previously described peptide from ant venom and here denominated as Bm-ponericin-L1. The antibacterial activity of Bm-ponericin-L1 was determined against ESKAPE pathogens. Scanning electron microscopy confirmed the membrane disruption potential of Bm-ponericin-L1. Moreover, this peptide also showed promising antibiofilm activity. Finally, cell viability and hemolytic assays revealed that Bm-ponericin-L1 is non-toxic toward primary fibroblasts cell lines and red blood cells, respectively. This study opens up new perspectives toward an alternative approach to overcoming multiple-antibiotic-resistance by means of AMPs through invertebrates' infection with human pathogenic bacteria., (© 2022. The Author(s).)

Streptomyces strains are powerhouses for a diverse range of secondary metabolites, including antibiotics, anticancer and immunosuppressive agents, and enzymes. Here, we report the genome sequence of Streptomyces sp. strain PSAA01, which was isolated from a soil sample taken in Manas National Park, Assam, India, in the eastern Himalayan foothills of India.

Endometriosis is a benign gynecological condition characterized by increased growth, inflammation, invasion, and angiogenesis, partly regulated by a class of enzymes called matrix metalloproteinases (MMPs). The importance of a few MMPs, e.g., MMP-9, -3, and -7 has been studied in endometriosis progression. Although MMP-13 plays an essential role in bone regeneration and cancer, no report has been found on the part of MMP-13 and endometriosis progression. We found the upregulation of MMP-13 expression and activity in patients having endometriosis in the eastern Indian population. In addition, the -77A/G polymorphism of the MMP13 promoter (rs: 2252070) is associated with regulating transcription and subsequent susceptibility to disease. In eastern Indian case-control groups, the effect of the -77A/G single-nucleotide polymorphism on MMP13 promoter activity and its relationship with endometriosis susceptibility was studied. The AG genotype was shown to be more predisposed to endometriosis risk than the GG genotype (p: 0.02; odds ratio [OR]: 1.65, 95% confidence interval [CI]: 1.10-2.49), also AG genotype was more frequent in late-stage patients compared to early-stage (p: 0.03, OR: 2.0, 95% CI: 1.09-3.66). Furthermore, the MMP13 gene levels were greater in AA compared to GG individuals. Additionally, MMP13 promoter-reporter experiments in cultured endometrial epithelial cells and in silico analyses both demonstrated increased transcriptional activity near the G to A transition under basal/IL-1β -induced/c-FOS overexpressed condition. Overall, c-FOS tighter binding to the A allele-carrying promoter enhances MMP13 transcription, which is further amplified by IL-1β due to increased c-FOS phosphorylation, promoting MMP-13 production and endometriosis risk., (© 2022 Wiley Periodicals LLC.)

Aim: This study investigated the link between forced swim induced acute gastric ulceration, inflammation and MMP-3 along with the possible mechanism of protective efficacy of melatonin., Main Methods: We distributed Balb/c mice into four different groups. Group 1 and 2 were given PBS gavage. Group 3 and 4 were given melatonin (60 mg/kg b.wt.) and omeprazole (25 mg/kg b.wt.), respectively, an hour prior to forced swim. Ulcer index, tissue histology, immunohistochemistry, protein carbonylation, lipid peroxidation, Myeloperoxidase, Zymography, Western blotting, reactive oxygen species (ROS), mitochondrial dehydrogenase, mitochondrial transmembrane potential and bioinformatical analysis were performed., Key Findings: Our data revealed that gastric ulceration due to forced swim stress is responsible for overproduction of ROS, which may be a prime reason for mitochondrial dysfunction and induction of apoptosis via activation of Caspase-3. ROS is also responsible for p38 phosphorylation which in turn increases the activity of MMP-3 in ulcerated milieu, along with the oxidation of proteins, peroxidation of lipids and altered expression patterns of heat shock protein (HSP)-70. Melatonin is shown to reduce the inflammatory burden in gastric milieu and offers gastroprotection by binding to the active site of MMP-3; thereby inhibiting its activity, as suggested by in silico studies. Melatonin also inhibits the downregulation of HSP-70 and activates p38 dephosphorylation and thereby, it rescues gastric mucosal cells from stress-induced ulceration., Significance: Our findings suggest that, melatonin imparts its gastroprotective effect by down-regulating the activation of MAPK-ERK pathway along with binding to the active site of MMP-3., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The discovery of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and its associated Cas endonucleases in bacterial and archaeal species allowed scientists to modify, utilized, and revolutionize this tool for genetic alterations in any species. Especially the type II CRISPR-Cas9 system has been extensively studied and utilized for precise and efficient DNA manipulation in plant and mammalian systems over the past few decades. Further, the discovery of the type V CRISPR-Cas12 (Cpf1) system provides more flexibility and precision in DNA manipulation in prokaryotes, plants, and animals. However, much effort has been made to employ and utilize the above CRISPR tools for RNA manipulation but the ability of Cas9 and Cas12 to cut DNA involves the nuisance of off-target effects on genes and thus may not be employed in all RNA-targeting applications. Therefore, the search for new and diverse Cas effectors which can precisely detect and manipulate the targeted RNA begins and this led to the discovery of a novel RNA targeting class 2, type VI CRISPR-Cas13 system. The CRISPR-Cas13 system consists of single RNA-guided Cas13 effector nucleases that solely target single-stranded RNA (ssRNA) in a programmable way without altering the DNA. The Cas13 effectors family comprises four subtypes (a-d) and each subtype has distinctive primary sequence divergence except the two consensuses Higher eukaryotes and prokaryotes nucleotide-binding domain (HEPN) that includes RNase motifs i.e. R-X4-6-H. These two HEPN domains are solely responsible for executing targetable RNA cleavage activity with high efficiency. Further, recent studies have shown that Cas13d exhibits higher efficiency and specificity in cleaving targeted RNA in the mammalian system compared to other Cas13 endonucleases of the Cas13 enzyme family. In addition to that, Cas13d has shown additional advantages over other Cas13 variants, structurally as well as functionally which makes it a prominent and superlative tool for RNA engineering and editing. Therefore considering the advantages of Cas13d over previously characterized Cas13 subtypes, in this review, we encompass the structural and mechanistic properties of type VI CRISPR-Cas13d systems, an overview of the current reported various applications of Cas13d, and the prospects to improve Cas13d based tools for diagnostic and therapeutic purposes., 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., (Copyright © 2022 Gupta, Ghosh, Chakravarti, Singh, Ravichandiran, Swarnakar and Ghosh.)

This paper primarily discusses the structural performance analysis of a single/double/quadruple tapered optical fiber (TOF) structure based on single-mode fiber (SMF) and multi-mode fiber (MMF). Furthermore, the TOF's performance, including its diameter distribution, transmitted intensity, and reproducibility, is also evaluated. According to the experimental results, it can be concluded that the quadruple TOF structure based on SMF has a higher density of evanescent waves (EWs) on the surface of the tapered area, which is essential for the fabrication of high-sensitivity optical fiber sensors. The structure proposed in this article is feasible, and it can be used for optical fiber sensing while offering significant practical and promising applications as well.

The gastrointestinal (GI) tract is one of the major sites for reactive oxygen species generation (ROS). Physiological ROS, lower than the threshold concentration, is beneficial for human physiology to preserve gut functional integrity. However, ROS generated in large quantities in presence of external stimuli overwhelms the cellular antioxidant defense mechanism and results in oxidative damage and associated physiological disorder. Graphene quantum dots (GQDs) are a class of carbon-based nanomaterials that have attracted tremendous attention not only for their tunable optical properties but also for their broad-spectrum antioxidant properties. In this report we have shown that GQDs are highly efficient in scavenging ROS and suppressing stress-induced gastric ulcers by targeting the MMP-9 pathway and reducing the inflammatory burden by suppressing excessive oxidative stress by inducing high caspase activity, overproduction of Bax, and downregulation of BCL2., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The healing of damaged tissues in gastric tract starts with the extracellular matrix (ECM) remodeling by the action of matrix metalloproteinases (MMPs). Particularly, MMP-2 (gelatinase-A) maintains ECM structure and function by degrading type IV collagen, the major component of basement membranes and by clearing denatured collagen. The proteolytic activities of MMPs are critically balanced by endogenous tissue inhibitors of metalloproteinases (TIMPs) and disruption of this balance results in several diseases. The well-known drug omeprazole is a proton pump inhibitor used for curing gastric ulcer. However, the action of omeprazole in ECM remodeling on gastroprotection has never been explored. Herein, using rat model of gastric ulcer, we report that restraint cold stress caused increase apoptosis to surface epithelia of gastric tissues along with TIMP-3 upregulation and inhibition of MMP-2 activity thereon. In contrast, omeprazole treatment suppressed TIMP-3 while increasing MMP-2 activity and thereby, restoring MMP-2/TIMP-3 balance. Additionally, nanomolar binding constant (K d  = 318 nM) of omeprazole with purified MMP-2 indicates a direct effect of omeprazole in restoring MMP-2 activity. Further in silico simulations revealed a plausible mechanism of action of omeprazole for TIMP-3 deactivation. Altogether, omeprazole restores MMP-2 activity and reduces apoptosis while preventing acute stress-induced gastric ulcer that occurs via suppression of nuclear factor kappa B (NF-κB) activity and peroxisome proliferator-activated receptor gamma activity (PPAR-γ). This represents an unprecedented correlation between physical docking of drug molecule to a protease and the severity of organ injury and provides a novel therapeutic approach to prevent stress induced tissue damage., (Copyright © 2022 Elsevier Inc. All rights reserved.)

All-optical logic gates are exceptionally suited for Boolean ultrahigh-speed operation and logical computing. This study presents a plasmonic model that uses a Y-shaped metal-insulator-metal waveguide structure that realizes the ultrafast all-optical AND, XOR, and XNOR gate operation that is developed at a footprint of 6.6µ m ×3.4µ m with a wavelength of 1.55 µm. This construction relies on the notion of linear interference. The insertion loss and extinction ratio of the model are observed as 1.49 dB and 21.49 dB for AND, 1.03 dB and 18.97 dB for XOR, and 2.06 dB, and 10.92 dB for XNOR, respectively. The transmission efficiency, response time, and speed of the structure also are calculated and are used to improve the performance of any complex circuit in the future. The theoretical analysis of the proposed structure is carried out using the finite-difference time-domain method.

Gene expression can be regulated by small non-coding RNA molecules like microRNAs (miRNAs) which act as cellular mediators necessary for growth, differentiation, proliferation, apoptosis, and metabolism. miRNA deregulation is often observed in many human malignancies, acting both as tumor-promoting and suppressing, and their abnormal expression is linked to unrestrained cellular proliferation, metastasis, and perturbation in DNA damage as well as cell cycle. Matrix Metalloproteases (MMPs) have crucial roles in both growth, and tissue remodeling in normal conditions, as well as in promoting cancer development and metastasis. Herein, we outline an integrated interactive study involving various MMPs and miRNAs and also feature a way in which these communications impact malignant growth, movement, and metastasis. The present review emphasizes on important miRNAs that might impact gynecological cancer progression directly or indirectly via regulating MMPs. Additionally, we address the likely use of miRNA-mediated MMP regulation and their downstream signaling pathways towards the development of a potential treatment of gynecological cancers., 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., (Copyright © 2022 Pandit, Begum, Saha, Srivastava and Swarnakar.)

In this paper, a three-input AND logic gate is employed using a 2D photonic crystal T-shaped waveguide using a silicon in an air medium. In contrast to other gates, the key functions of employing an AND gate are recognition, error correction, code conversion, data encryption/decryption, and arithmetic operations. The proposed footprint is 8.4µ m ×5.4µ m , which is a modest size. The performance of the proposed AND gate is investigated by employing the finite-difference time-domain approach, and the outputs are validated at wavelength ( λ ) of 1.55 µm. The outcomes clearly show the higher contrast ratio (CR) of 24.533 dB, and the worst case CR of is 8.6 dB; transmission efficiency values for minimum and maximum values are 19.6% and 142%; reaction time is 26 fs; insertion loss is 1.52 dB; and bit rate is 38.4 Tbps, which can be used in high-speed optical signal processing. The suggested circuit's primary objective is to consume minimal space and possess high CR.

Zymography is a powerful technique for the assay of different hydrolases that act upon any biological macromolecule. In particular, zymography is used to assay the activities of serine proteases, e.g., matrix metalloproteinases (MMPs), and reverse zymography is used for tissue inhibitors of metalloproteinases (TIMPs) in multifarious experimental samples. Zymography is a method of electrophoretic separation of proteases under non-reducing conditions in a polyacrylamide gel containing substrate. The resolved proteins are renatured by exchange of the anionic detergent with a nonionic one, and the gel is incubated in a specific buffer for the specific proteases. After staining the gel by Coomassie blue staining solution, the proteolytic activities are visualized as clear colorless bands against a dark background. In contrast, reverse zymography is a parallel technique to detect protease inhibitors. In addition to substrate gelatin, proteases (i.e., MMPs) are also incorporated in proper ratio into the polyacrylamide gel. After electrophoresis, during the developing step, the MMPs specifically digest the substrate in regions where TIMPs are absent. Thus, inhibitors/TIMP is represented as dark zones of inhibition against a transparent background after staining. In this chapter, common troubleshoots during sample preparation, running zymography, and data interpretation are discussed. Notes are specified to enhance the sensitivity of the methods. In conclusion, zymography could be crucial for enzyme assay at the nanogram level and for the improvement of new investigative techniques for diseases such as endometriosis, rheumatoid arthritis, osteoarthritis, tumor invasion, and inflammation., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Periodontitis is a multifactorial host-mediated oral disease caused by microbes. Previous studies suggested that interleukin-6 (IL-6) gene promoter polymorphism (-174G > C) are associated with the risk of periodontitis, although the results were inconclusive. This study investigated the association between IL-6 -174G > C polymorphism and susceptibility to periodontitis., Method: A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and Google Scholar databases to retrieve relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association between 174G > C polymorphism and the risk of periodontitis. Cochrane Q and I 2 statistics were used to measure heterogeneity between studies. Publication bias was estimated using Begg's funnel plots and Egger's test., Results: Our results showed significant differences in the allelic (C vs. G: OR = 0.82, CI = 0.65-1.03), recessive (CC vs. GC + GG: OR = 0.69, CI = 0.42-1.13), and dominant (GC + CC vs. GG: OR = 0.85, CI = 0.63-1.13) genetic models of the IL6 -174G > C polymorphism and risk of periodontitis. Further, subgroup analysis showed decreased susceptibility to periodontitis associated with IL6 -174 G > C in a Brazilian population (C vs. G: OR = 0.60, CI = 0.41-0.88; GC + CC vs. GG: OR = 0.57, CI = 0.42-0.78) but not in Asian or Caucasian populations., Conclusion: The findings of this study revealed that the IL6 -174 "C" allele is protective against periodontitis in the Brazilian population., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2021 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Gynecological illness accounts for around 4.5% of the global disease burden, which is higher than other key global health concerns such as malaria (1.04%), TB (1.9%), ischemic heart disease (2.2%), and maternal disorders (3.5%). Gynecological conditions in women of reproductive age are linked to both in terms of diagnosis and treatment, especially in low-income economies, which poses a serious social problem. A greater understanding of health promotion and illness management can help to prevent diseases in gynecology. Due to the lack of established biomarkers, the identification of gynecological diseases, including malignancies, has proven to be challenging in most situations, and histological exams remain the gold standard. Metalloproteinases (MMPs, ADAMs, ADAMTSs) and their endogenous inhibitors (TIMPs) modulate the protease-dependent bioavailability of local niche components (e.g., growth factors), matrix turnover, and cellular interactions to govern specific physical and biochemical characteristics of the environment. Matrix metalloproteinases (MMPs), A Disintegrin and Metalloproteinase (ADAM), and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) are zinc-dependent endopeptidases that contribute significantly to the disintegration of extracellular matrix proteins and shedding of membrane-bound receptor molecules in several diseases, including arthritis. MMPs are noteworthy genes associated with cancer development, functional angiogenesis, invasion, metastasis, and immune surveillance evasion. These genes are often elevated in cancer and multiple benign gynecological disorders like endometriosis, according to research. Migration through the extracellular matrix, which involves proteolytic activity, is an essential step in tumor cell extravasation and metastasis. However, none of the MMPs' expression patterns, as well as their diagnostic and prognostic potential, have been studied in a pan-cancer context. The latter plays a very important role in cell signaling and might be used as a cancer treatment target. ADAMs are implicated in tumor cell proliferation, angiogenesis, and metastasis. This review will focus on the contribution of the aforementioned metalloproteinases in regulating gynecological disorders and their subsequent manipulation for therapeutic intervention., 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., (Copyright © 2021 Begum, Pandit and Swarnakar.)

Hepatic miRNA, miR-122, plays an important role in controlling metabolic homeostasis in mammalian liver. Intercellular transfer of miR-122 was found to play a role in controlling tissue inflammation. miR-122, as part of extracellular vesicles released by lipid-exposed hepatic cells, are taken up by tissue macrophages to activate them and produce inflammatory cytokines. Matrix metalloprotease 2 or MMP2 was found to be essential for transfer of extracellular vesicles and their miRNA content from hepatic to non-hepatic cells. MMP2 was found to increase the movement of the extracellular vesicles along the extracellular matrix to enhance their uptake in recipient cells. Inhibition of MMP2 restricts functional transfer of hepatic miRNAs across the hepatic and non-hepatic cell boundaries, and by targeting MMP2, we could reduce the innate immune response in mammalian liver by preventing intra-tissue miR-122 transfer. MMP2 thus could be a useful target to restrict high-fat-diet-induced obesity-related metaflammation., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

The emergence of SARS-CoV-2 has brought the world to a standstill, and till date, effective treatments and diagnostics against this idiosyncratic pathogen are lacking. As compared to the standard WHO/CDC qPCR detection method, which consumes several hours for detection, CRISPR-based SHERLOCK, DETECTR, and FELUDA have emerged as rapid diagnostic tools for the detection of the RNA genome of SARS-CoV-2 within an hour with 100% accuracy, specificity, and sensitivity. These attributes of CRISPR-based detection technologies have taken themselves one step ahead of available detection systems and are emerging as an inevitable tool for quick detection of the virus. Further, the discovery of Cas13s nucleases and their orthologs has opened a new corridor for exploitation of Cas13s as an antiviral therapy against SARS-CoV-2 and other viral diseases. One such approach is Prophylactic Antiviral CRISPR in huMAN cells (PACMAN), which needs a long haul to bring into therapy. The approval of SHERLOCK as the first CRISPR-based SARS-CoV-2 test kit by the FDA, for emergency diagnosis of COVID-19 patients, has given positive hope to scientists that sooner human trials of CRISPR-based therapy will be ratified. In this review, we have extensively reviewed the present CRISPR-based approaches, challenges, and future prospects in the light of diagnostics and therapeutics against SARS-CoV-2. KEY POINTS: • The discovery of Cas12 and Cas13 siblings allowed scientists to detect the viral genes. • Cas13d's identification aided scientists in precisely cleaving the SARS-CoV-2 ssRNA. • CRISPR-Cas system acts as "molecular detector and antiviral proctor.", (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a novel variant of coronavirus has emerged from Wuhan in China and has created havoc impulses across the world with a larger number of fatalities. At the same time, studies are on roll to discover potent vaccine against it or repurposing of approved drugs which are widely adopted are under trial to eradicate the SARS-CoV-2 causing COVID-19 pandemic. Reports have also shown that there are asymptomatic carriers of COVID-19 disease who can transmit the disease to others too. However, the first line defense of the viral attack is body's strong and well-coordinated immune response producing excessive inflammatory innate reaction, thus impaired adaptive host immune defense which lead to death upon the malfunctioning. Considerable works are going on to establish the relation between immune parameters and viral replication that, might alter both the innate and adaptive immune system of COVID-19 patient by up riding a massive cytokines and chemokines secretion. This review mainly gives an account on how SARS-CoV-2 interacts with our immune system and how does our immune system responds to it, along with that drugs which are being used or can be used in fighting COVID-19 disease. The curative therapies as treatment for it have also been addressed in the perspective of adaptive immunity of the patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: Matrix metalloproteinases (MMPs) are a group of host-derived zinc-dependent enzymes which mediates the destruction of the extracellular matrix. In periodontitis, there is excess production of MMPs associated with periodontal tissue destruction. The aim of this study was to estimate the level MMP-9 in both active and latent form in gingival tissue (GT) samples collected from periodontitis patients with different rates of progression and compare it with healthy individuals., Materials and Methods: Sixty patients were selected and divided into three groups, 20 each: Group A (slowly/moderately progressing periodontitis), Group B (rapidly progressing periodontitis), and Group C (clinical periodontal health). Plaque index, gingival index, periodontal probing depth (PPD), and clinical attachment level were recorded. GT samples were collected from all 60 patients and MMP-9 expressions were measured using gelatin zymography and western blotting., Results: Levels of active MMP-9 (aMMP-9) and latent MMP-9 (lMMP-9) were significantly high in both Group A (GA) (aMMP-9: 2.05 arbitrary unit [AU]/lMMP-9: 2.54 AU) and Group B (GB) (aMMP-9: 1.32 AU/lMMP-9: 1.74 AU) when compared to that of Group C (GC) (aMMP-9: 0.93/lMMP-9: 1.08 AU). In GA, levels of aMMP-9 showed a significant correlation with PPD values. No other correlations were found., Conclusion: The levels of aMMP-9 and lMMP-9 were increased in both the types of periodontitis when compared with periodontally healthy individuals. A significant correlation was found between PPD and activities of aMMP-9 in slowly/moderately progressing periodontitis patients. However, further studies are required to confirm these findings., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Society of Periodontology.)

The discovery of CRISPR-Cas9 system has revolutionized the genome engineering research and has been established as a gold standard genome editing platform. This system has found its application in biochemical researches as well as in medical fields including disease diagnosis, development of therapeutics, etc. The enormous versatility of the CRISPR-Cas9 as a high throughput genome engineering platform, is derailed by its off-target activity. To overcome this, researchers from all over the globe have explored the system structurally and functionally and postulated several strategies to upgrade the system components including redesigning of Cas9 Nuclease and modification of guide RNA(gRNA) structure and customization of the protospacer adjacent motif. Here in this review, we portray the comprehensive overview of the strategies that has been adopted for redesigning the CRISPR-Cas9 system to enhance the efficiency and fidelity of the technology., Competing Interests: Conflict of interest The authors declare that there was no conflict of interest., (© 2021 Elsevier Inc. All rights reserved.)