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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.)

Reversible logic gates are capable of designing lossless digital systems, which have received a great deal of attention in photonic integrated circuits due to their advantages, such as less heat generation and low power dissipation. In this paper, all-optical reversible Feynman and Toffoli logic gates are designed for optical computing devices and low-power integrated circuits. Proposed designs of all-optical reversible logic gates are implemented with two-dimensional photonic crystal waveguides without using any nonlinear material. The finite-difference time-domain method is used to simulate and verify the proposed design, and it is operated at a wavelength of 1550 nm. The structure of all-optical reversible logic gates requires much less area, and Feynman logic gates offer a contrast ratio (CR) of 12.4 dB, transmittance of 0.96, and less insertion loss of -0.015 d B , while Toffoli logic gates offer a CR of 32.5 dB, transmittance of 0.9, and less insertion loss of -0.04 d B .

The performance of an ultra-compact all-optical D flip-flop using photonic crystal waveguides is numerically analyzed and examined by optimized parameters such as refractive index and silicon rod radius. In the field of optical networking and computing, flip-flops are used to reduce the complexity of digital circuits. The phenomenon of optical interference effect is used to implement a D flip-flop at a wavelength of 1550 nm. This structure is designed using T-shaped waveguides without using non-linear material. The proposed design is small, has low insertion losses of 0.087 dB when operated at low power level, and provides high contrast ratio of 25 dB and transmission ratio of more than 96%.

A series of heterocyclic C5-curcuminoids (bis(arylmethylidene)acetones) (PJ1-PJ6) having a large Stokes shift (Δλ = 104-173 nm) have been synthesized for the selective detection of cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) in living cells. The compounds were synthesized using a new methodology via deacetylation under microwave conditions. The photophysical properties of these compounds have been studied. Prominent colour changes from bright yellow to colourless in the presence of thiols were observed for PJ1. Live cell imaging has been employed with PJ1 for the utilization of the probe to detect homocysteine in A375 cells and apoptosis in AGS cells.

Melatonin is a secretory product of the pineal gland that regulates circadian rhythm. It is also well-known for its anti-inflammatory and antioxidant properties against the damaging influences of reactive oxygen species. To improve its therapeutic efficacy, a new formulation with melatonin loaded in a stimuli-responsive polymeric nanocapsule has been prepared following an inverse mini-emulsion technique. The colloidal stability of the melatonin-loaded nanocapsules (MNCs) is studied using dynamic light scattering, while the morphology of these MNCs is characterized using various electron microscopies. These MNCs have an inner diameter of 80-120 nm with a cell wall thickness of 29 ± 11 nm. The emission band maximum for melatonin appears at 350 nm following excitation at 305 nm (quantum yield, Φ 350 = 0.13). The self-quenching nature of the entrapped melatonin molecules inside the nanocapsules attributes to a lower Φ 350 value for the MNCs. The controlled release of melatonin from MNCs in an in vitro condition is achieved by inducing a rupture of the polymeric backbone through maintaining a certain media pH (∼2.0-4.0) as an external stimulus, and this accounts for a significant enhancement in its characteristic luminescence. The H,K-ATPase, an integral membrane protein, maintains this specific pH range in the interior of the gastrointestinal tract. This methodology is adopted for developing an efficient drug delivery process in the gastric environment. A significant improvement in the AGS cell survival under oxidative stress conditions is observed during preincubation with MNCs compared to free melatonin. In a murine model of the stress-induced gastric ulcer, MNCs outperformed free melatonin in terms of drug efficacy. The value for the gastric ulcer index is reduced from ∼30 to ∼15 by free melatonin and from ∼30 to ∼8 by MNCs treatments, respectively. Such formulation could be a step forward for developing more efficient melatonin-based gastroprotective supplements.

MMP (matrix metalloproteinase)-7-a potent extracellular matrix degrading enzyme-is emerging as a new regulator of cardiovascular diseases. However, potential contributions of MMP7 genetic variations to hypertension remain unknown. In this study, we probed for the association of a tag single-nucleotide polymorphism in the MMP7 promoter (-181A/G; rs11568818) with hypertension in an urban South Indian population (n=1501). The heterozygous AG genotype significantly increased risk for hypertension as compared with the wild-type AA genotype (odds ratio, 1.60 [95% CI, 1.25-2.06]; P =2.4×10 -4 ); AG genotype carriers also displayed significantly higher diastolic blood pressure and mean arterial pressure than wild-type AA individuals. The study was replicated in a North Indian population (n=949) (odds ratio, 1.52 [95% CI, 1.11-2.09]; P =0.01). Transient transfection experiments using MMP7 promoter-luciferase reporter constructs revealed that the variant -181G allele conferred greater promoter activity than the -181A allele. Computational prediction and structure-based conformational and molecular dynamics simulation studies suggested higher binding affinity for the CREB (cyclic AMP response element-binding protein) to the -181G promoter. In corroboration, overexpression/downregulation of CREB and chromatin immunoprecipitation experiments provided convincing evidence for stronger binding of CREB with the -181G promoter. The -181G promoter also displayed enhanced responses to hypoxia and epinephrine treatment. The higher promoter activity of -181G allele translated to increased MMP7 protein level, and MMP7 - 181AG heterozygous individuals displayed elevated plasma MMP7 levels, which positively correlated with blood pressure. In conclusion, the MMP7 A-181G promoter polymorphism increased MMP7 expression under pathophysiological conditions (hypoxic stress and catecholamine excess) via increased interactions with CREB and enhanced the risk for hypertension in its carriers.

Abstract: Tea polyphenols are known to prevent various ailments like cancer, atherosclerosis, hypertension and diabetes. Our study aimed at to decipher the gastroprotective effect of aqueous black tea extract (BTE) against ethanol-induced gastric damage and the role of BTE in modulating MMP-9 activity and expression, both in vivo and in vitro. The protective role of BTE was assessed in Sprague-Dawley rats after inducing damage with 70% ethanol. Human gastric adenocarcinoma cells (AGS) were treated with ethanol in ex vivo experiment. MMP-9 activity and expression were investigated through gelatin zymography and western blotting. Reactive oxygen species (ROS) generation was also studied by fluorescence spectroscopy and confocal microscopy, with or without treatment of BTE both in vivo and in vitro experiments. In addition, the effect of citric acid treated BTE (cBTE), which mimics lemon tea, was examined on ethanol-induced gastropathy. BTE exhibited antiulcer activity through reduction of glutathione depletion, lipid peroxidation, protein oxidation, ROS production and inflammatory cell infiltration in rat gastric tissues. In addition, BTE significantly inhibited synthesis and secretion of proMMP-9 both in vivo and in vitro. The mitochondrial enzymes succinate dehydrogenase and NADH oxidase in rat gastric tissues were downregulated by BTE while protecting gastric ulcer. Citric acid addition to BTE was observer to enrich the lead compound, catechin. Interestingly, cBTE showed higher anti-ulcer activity than the untreated one. BTE shows protective role against ethanol-induced gastric ulcer in rats through scavenging ROS and downregulating proMMP-9 activity. While cBTE shows better protection due to enrichment of catechin and removal of tannins in tea extract leading to enhanced inhibitory role on proMMP-9 activity and ROS production., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Clinical Biochemists of India 2018.)

Cerebral ischemia-reperfusion (CIR) accelerates the progression of neurodegeneration by causing mitochondrial dysfunction to overproduce reactive oxygen species (ROS). Curcumin shows protective effects against CIR-induced oxidative damage. Free curcumin (FC) is effective at high doses due to its poor bioavailability. Also the blood-brain barrier (BBB) limits the passage of substances from circulation into the cerebral region. Thus, formulation of curcumin within polyethylene glycol (PEG)-ylated polylactide-co-glycolide (PLGA) nanoparticles (NC) was applied orally to aged rats to explore its role against CIR injury. Mitochondrial damage was evaluated. The levels of pro-inflammatory cytokines and components of apoptotic pathway were studied. Unlike FC, NC pre-treatment exerted better neuro-protection by ameliorating ROS-mediated oxidative damage and prevented CIR-induced neuronal apoptosis. Therefore, curcumin incorporated PEGylated PLGA nanoparticles may be used as a suitable delivery vehicle to the brain as they can increase curcumin bioavalability and the released curcumin may confer protection to the neurons against CIR-induced oxidative damage., (Copyright © 2018 Elsevier B.V. All rights reserved.)

PC, PCM, PCS, and PCMS are our designed & synthesized ∼8 nm PAMAM dendrimer (P) -based organic supramolecular systems, for example, PCMS has 32 molecular motors (M), 4 pH sensors (S) and 2 multi-level molecular electronic switches (C). We have reported earlier following a preliminary in-vitro test that the synthesized PCMS can selectively target cancer cell nucleotides if triggered wirelessly by an electromagnetic pulse. Here to further verify its drug potential, we have studied the preliminary efficacy, toxicity, and pharmacokinetics of P derivatives (PC, PCM, PCMS) in-vivo and in-vitro. We used ethanol-induced gastric inflammation model and cultured human gastric epithelial cells AGS to examine to the toxicity of PAMAM dendrimers cell permeability and toxicity, in (a) the cultured human gastric epithelium cells (AGS), and in (b) the gastric ulcer mice model. Here we report that the toxicity of PAMAM dendrimer (>G3.5) P can be reduced by adding C, M and S. Gastric ulcer is the primary stage of the manifestation of acute inflammation, even gastric epithelial cancer. Ethanol causes ulceration (ulcer index 30), thus upregulates both pro and active MMP-9. A 50 μl PCMS dose prior to ethanol administration reduces ulceration by ∼80% and downregulates MMP-9 and prevents oxidative damages of gastric tissue by ECM remodeling. Alcohol's inflammation of mouse stomach causes up-regulation of both pro and active MMP-9, resulting in oxidative damages of gastric tissue by ECM remodeling. PCMS in particular dose window reverses & alters ECM remodeling, thus, neutralizing alcohol-induced inflammation & generation of ROS.

Cancer development and metastasis are associated to perturbation in metabolic functions of tumor cells and surrounding inflammatory and stromal cell responses. Eicosanoids and lipid mediators, in this regard, attract potential attention during cancer development. Eicosanoids, which include prostaglandin, prostacyclin, thromboxane, and leukotriene, are synthesized from arachidonic acid when cells are stimulated by stress, cytokines, or other growth factors. However, the underlying mechanism of eicosanoids in cancer development, specially their interactions with proto-oncogene factors in tumor microenvironment, remain unexplored. On the other hand, matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases which are involved in degradation of different extracellular matrix (ECM) proteins. MMPs are associated with different physiological responses, including embryogenesis, vasculogenesis, and cellular remodeling, as well as different disease pathogenesis. Induced MMP responses are especially associated with cancer metastasis and secondary tumor development through proteolytic cleavage of several ECM and non-ECM proteins. Although both eicosanoids and MMPs are involved with cancer progression and metastasis, the interrelation between these two molecules are less explored. The present review discusses relevant studies that connect eicosanoids and MMPs and highlight the crosstalk between them offering novel therapeutic approach in cancer treatment.

Endometriosis, characterized by extrauterine development of endometrial glands and stroma, is associated with increased risk of ovarian cancer development. In the present study, we investigated the role of matrix metalloproteinase-7 (MMP-7) on epithelial-mesenchymal transition (EMT) during ovarian endometriosis ( N = 40) progression. We found that the expressions of EMT markers such as vimentin, slug, and N-cadherin were significantly elevated in late stages of ovarian endometriosis compared with those found in early stages. In addition, the activity and expression of ectopic MMP-7 were significantly higher in the late stages of endometriosis. In vitro studies revealed that increased expression of MMP-7 as well as epidermal growth factor (EGF), which was significantly elevated in severe stages of ovarian endometriosis, induced EMT in endocervical epithelial cells (End1/E6E7). Silencing the MMP-7 transcripts using small interfering RNA attenuated EMT responses, whereas treatment with recombinant active MMP-7 promoted EMT by cleaving E-cadherin. In addition, EGF receptor (EGFR) inhibitor treatments regressed endometriotic lesions and decreased MMP-7 activities in a mouse model of endometriosis. Chromatin immunoprecipitation assay identified EGFR-mediated ERK1 and activator protein 1 signaling for the transcriptional activation of MMP-7 in End1/E6E7 epithelial cells.-Chatterjee, K., Jana, S., DasMahapatra, P., Swarnakar, S. EGFR-mediated matrix metalloproteinase-7 up-regulation promotes epithelial-mesenchymal transition via ERK1-AP1 axis during ovarian endometriosis progression.

Formulated mesoporous silica nanoparticle (MSN) systems offer the best possible drug delivery system through the release of drug molecules from the accessible pores. In the present investigation, steady state and time resolved fluorescence techniques along with the fluorescence imaging were applied to investigate the interactions of dye loaded MSN with fluorescent unilamellar vesicles and live cells. Here 1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC) was used to prepare Small Unilamellar Vesicles (SUVs) as the model membrane with fluorescent 1,6-diphenyl-1,3,5-hexatriene (DPH) molecule incorporated inside the lipid bilayer. The interaction of DPH incorporated DMPC membrane with Fluorescein loaded MSN lead to the release of Fluorescein (Fl) dye from the interior pores of MSN systems. The extent of release of Fl and spatial distribution of the DPH molecule has been explored by monitoring steady-state fluorescence intensity and fluorescence lifetime at physiological condition. To investigate the fate of drug molecule released from MSN, fluorescence anisotropy has been used. The drug delivery efficiency of the MSN as a carrier for doxorubicin (DOX), a fluorescent chemotherapeutic drug, has also been investigated at physiological conditions. The study gives a definite confirmation for high uptake and steady release of DOX in primary oral mucosal non-keratinized squamous cells in comparison to naked DOX treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cerebral ischemia-reperfusion (CIR) injury occurs as a result of oxygen occlusion in the carotid artery through embolus or thrombus formation or cerebrovascular hemorrhage. The oxygen thrust during reperfusion causes the generation of reactive oxidative species (ROS) which exert a potential threat to neuronal survival. ROS may possibly be arrested by antioxidants. After CIR, extracellular matrix remodeling takes place, which is governed by matrix metalloproteinases (MMPs). Augmentation of lipid per oxidation, perturbation of antioxidant enzyme activities and the loss of pyramidal neuronal cells in rat brain were attributed to CIR injury. Melatonin can readily cross the blood-brain barrier (BBB) to exert protective effects as an antioxidant but it is quickly cleared by the circulating blood. Also melatonin is easily degraded by light and hence is found to be ineffective during daytime. Results of the present study showed that unlike free melatonin (FM), the application of nanocapsulated melatonin (NM) exhibited significantly higher potential even at much lower concentrations to rescue neuronal cells and mitochondria during CIR insult and also restored the activities of antioxidative enzymes and MMPs to their normal levels. Hence, nanoencapsulated melatonin may be considered as a suitable drug delivery system for brain to exert protection against CIR injury., (Copyright © 2017. Published by Elsevier Inc.)

Neem (Azadirachta indica) is a well-known medicinal and insecticidal plant. Although previous studies have reported the antiulcer activity of neem leaf extract, the lead compound is still unidentified. The present study reports tamarixetin 3-O-β-d-glucopyranoside (1) from a methanol extract of neem leaves and its gastroprotective activity in an animal model. Compound 1 showed significant protection against indomethacin-induced gastric ulceration in mice in a dose-dependent manner. Moreover, ex vivo and circular dichroism studies confirmed that 1 inhibited the enzyme matrix metalloproteinase-9 (MMP-9) activity with an IC 50 value of ca. 50 μM. Molecular docking and dynamics showed the binding of 1 into the pocket of the active site of MMP-9, forming a coordination complex with the catalytic zinc, thus leading to inhibition of MMP-9 activity.

Background: Helicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation. Coinfection with H. pylori strain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects of H. pylori infection by both cag + strain (SS1) and cag - strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa., Results: Mice infected with AM1/SS1 strain exhibited less gastric inflammation and reduced proMMP9 and proMMP3 activities in gastric tissues as compared to SS1/SS1 and SS1/AM1 infected groups. The expression of both MMP9 and MMP3 followed similar trend like activity in infected tissues. Both Th1 and Th17 responses were induced by SS1 strain more profoundly than AM1 strain infection which induced solely Th1 response in spleen and gastric tissues. Moreover, IFN-γ, TNF-α, IL-1β and IL-12 were significantly downregulated in mice spleen and gastric tissues infected by AM1/SS1 compared to SS1/SS1 but not with SS1/AM1 coinfection. Surprisingly, IL-17 level was dampened significantly in AM1/SS1 compared to SS1/AM1 coinfected groups. Furthermore, number of Foxp3 + T-regulatory (Treg) cells and immunosuppressive cytokines like IL-10 and TGF-β were reduced in AM1/SS1 compared to SS1/SS1 and SS1/AM1 coinfected mice gastric tissues., Conclusions: These data suggested that prior H. pylori cag - strain infection attenuated the severity of gastric pathology induced by subsequent cag + strain in C57BL/6 mice. Prior AM1 infection induced Th1 cytokine IFN-γ, which reduced the Th17 response induced by subsequent SS1 infection. The reduced gastritis in AM1/SS1-infected mice might also be due to enrichment of AM1- primed Treg cells in the gastric compartment which inhibit Th1 and Th17 responses to subsequent SS1 infection. In summary, prior infection by non-virulent H. pylori strain (AM1) causes reduction of subsequent virulent strain (SS1) infection by regulation of inflammatory cytokines and MMPs expression.

Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression., Competing Interests: The authors have declared that no competing interests exist.

Effluent from tannery industries can significantly affect the aquatic environment due to the presence of a variety of recalcitrant components. The present study focuses on a comparative assessment of the toxic impacts of an untreated tannery effluent and membrane treated effluents using snail, Pila globosa as an aquatic model. Composite tannery effluent collected from a common effluent treatment plant was selected as the untreated effluent. To investigate the effect of treated effluents on the aquatic organism the effluent was treated by two ways, viz. a single stage microfiltration (MF) using ceramic membrane and a two-step process involving MF followed by reverse osmosis (RO). The whole body tissue, gonad and mantle of P. globosa were subjected to enzyme assays like superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GSH-GPx), glutathione S- transferase (GST), etc. for assessing toxic impact. Changes in the biochemical parameters like protein, carbohydrate and amino acid were observed including histological studies of gonad and mantle tissue upon treatment with tannery effluents. To examine potential DNA damage due to the exposure of the effluent, comet assay was conducted. The study revealed that with an exposure to the untreated effluent, activity of the antioxidant enzymes increased significantly while the protein and carbohydrate content reduced largely in the whole body tissue, gonad as well as mantle tissues of P. globosa. Histological study indicated considerable damage in the gonad and mantle tissues following exposure to the untreated effluent. Comet assay using hemolymph of P. globosa following exposure to tannery effluent, showed significant genotoxicity. Interestingly, compared to the untreated effluent, damaging effect was reduced in molluscs tissues when exposed to MF treated effluent and even lesser when exposed to MF+RO treated effluent. Apart from the reduced activities of oxidative stress enzymes, the protein, amino acid and carbohydrate content of molluscs exposed to both of the treated effluent were found close to that of control. Comet assay revealed no damage in the DNA for MF and MF+RO treated effluent indicating that the membrane based treatment procedure restores environmental condition to control level., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Extensive usage of pharmaceutical and personal care products (PPCPs) and their discharge through domestic sewage have been recently recognized as a new generation environmental concern which deserves more scientific attention over the classical environmental pollutants. The major issues of this type of effluent addressed in this study were its colour, triclosan and anionic surfactant (SDS) content. Samples of cosmetic effluent were collected from different beauty treatment salons and spas in and around Kolkata, India and treated in bioreactors containing a bacterial consortium isolated from activated sludge samples collected from a common effluent treatment plant. Members of the consortium were isolated and identified as Klebsiella sp., Pseudomonas sp., Salmonella sp. and Comamonas sp. The biotreated effluent was subjected to ultrafiltration (UF) involving indigenously prepared ceramic membranes in both side-stream and submerged mode. Analysis of the MBR treated effluent revealed 99.22%, 98.56% and 99.74% removal of colour, triclosan and surfactant respectively. Investigation of probable acute and chronic cyto-genotoxic potential of the untreated and treated effluents along with their possible participation in triggering oxidative stress was carried out with Heteropneustes fossilis (Bloch). Comet formation recorded in both liver and gill cells and micronucleus count in peripheral erythrocytes of individuals exposed to untreated effluent increased with duration of exposure and was significantly higher than those treated with UF permeates which in turn neared control levels. Results of this study revealed successful application of the isolated bacterial consortium in MBR process for efficient detoxification of cosmetic effluent thereby conferring the same suitable for discharge and/or reuse., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Recent evidences suggest that cerebral ischemia-reperfusion insult plays significant role in pathogenic diseases like Alzheimer's disease (AD) and other neurodegenerative diseases. Toxic reactive oxygen species (ROS) generated by induced oxidative stress in the episodes of cerebral ischemia-reperfusion (CIR) plays major role in neurodegeneration. As the prime source of ROS generation, neuronal mitochondria, the cellular energy metabolic centre experience severe damage because of CIR-induced oxidative stress. The process of mitochondrial dysfunction is accelerated by CIR that may pave the pathway for neurodegeneration in AD among aged individuals. Prevention of CIR injury may be a shunt in order to minimize the risk of dementia of Alzheimer's type in aged individuals. The use of chemical antioxidants in CIR is not suitable as the blood- brain barrier (BBB) doesn't allow the entry of molecules from blood circulation into the brain. Thus L-ascorbic acid loaded polylactide nanocapsules were prepared and fed orally to assess the role of nanocapsulated ascorbic acid (NAA) against CIR induced oxidative injury in mitochondrial region of rat brains. Mitochondrial injury was assessed by the extent of lipid peroxidation and in situ antioxidant enzyme status. The levels of cytochrome c (cyt c), cyclooxygenase- 2 (COX-2) and iNOS were determined. Results showed that in comparison to free ascorbic acid (AA), NAA exerted better protection to the brain mitochondria by preventing oxidative damage in ROS mediated CIR injury.

Blue green algae Anabaena sp. was cultivated in synthetic arsenite solution to investigate its bio-oxidation potential for arsenic species. Response surface methodology (RSM) was employed based on a 3-level full factorial design considering four factors, viz. initial arsenic (III) concentration, algal dose, temperature and time. Bio-oxidation (%) of arsenic (III) was considered as response for the design. The study revealed that about 100% conversion of As (III) to As (V) was obtained for initial As (III) concentration of 2.5-7.5 mg/L at 30 °C for 72 h of exposure using 3 g/L of algal dose signifying a unique bio-oxidation potential of Anabaena sp. The dissolved CO2 (DCO2) and oxygen (DO) concentration in solution was monitored during the process and based on the data, a probable mechanism was proposed wherein algal cell acts like a catalytic membrane surface and expedites the bio-oxidation process. Bioaccumulation of arsenic, as well as, surface adsorption on algal cell was found considerably low. Lipid content of algal biomass grown in arsenite solution was found slightly lower than that of algae grown in synthetic media. Toxicity effects on algal cells due to arsenic exposure were evaluated in terms of comet assay and chlorophyll a content which indicated DNA damage to some extent along with very little decrease in chlorophyll a content. In summary, the present study explored the potential application of Anabaena sp. as an ecofriendly and sustainable option for detoxification of arsenic contaminated natural water with value-added product generation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-β1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-β1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-β1 alone caused an ∼ 25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions ("spikes") containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼ 20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-β1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-β1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-β1. Critically, patients who survived had significantly higher GM-CSF/TGF-β1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-β1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-β1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS., (Copyright © 2015 the American Physiological Society.)

Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to play a pivotal role in cancer invasion. The -181A→G (rs11568818) polymorphism in the MMP7 promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of -181A→G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n = 520). The GG genotype as compared with the AA genotype was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p = 0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis revealed that tobacco enhanced the risk for cancer more markedly in AG and GG carriers. Activity and expression of MMP7 were significantly higher in GG than in AA carriers. In support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine-induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the -181G than the -181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)