Acetaminophen induces mitochondrial apoptosis through proteasome dysfunctions.

Acetaminophen is a known antipyretic and non-opioid analgesic for mild pain and fever. Numerous studies uncover their hidden chemotherapeutics applications, including chronic cancer pain management. Acetaminophen also represents an anti-proliferative effect in some cancer cells. Few studies also suggest that the use of Acetaminophen can trigger apoptosis and impede cellular growth. However, Acetaminophen's molecular potential and precise mechanism against improper cellular proliferation and use as an effective anti-proliferative agent still need to be better understood. Here, our current findings show that Acetaminophen induces proteasomal dysfunctions, resulting in aberrant protein accumulation and mitochondrial abnormalities, and consequently induces cell apoptosis. We observed that the Acetaminophen treatment leads to improper aggregation of ubiquitylated expanded polyglutamine proteins, which may be due to the dysfunctions of proteasome activities. Our in-silico analysis suggests the interaction of Acetaminophen and proteasome. Furthermore, we demonstrated the accumulation of proteasome substrates and the depletion of proteasome activities after treating Acetaminophen in cells. Acetaminophen induces proteasome dysfunctions and mitochondrial abnormalities, leading to pro-apoptotic morphological changes and apoptosis successively. These results suggest that Acetaminophen can induce cell death and may retain a promising anti-proliferative effect. These observations can open new possible molecular strategies in the near future for developing and designing specific and effective proteasome inhibitors, which can be helpful in conjugation with other anti-tumor drugs for their better efficiency.

Synchronization of Mycobacterium life cycle: A possible novel mechanism of antimycobacterial drug resistance evolution and its manipulation.

Mycobacterium Tuberculosis (Mtb) causing Tuberculosis (TB) is a widespread disease infecting millions of people worldwide. Additionally, emergence of drug resistant tuberculosis is a major challenge and concern in high TB burden countries. Most of the drug resistance in mycobacteria is attributed to developing acquired resistance due to spontaneous mutations or intrinsic resistance mechanisms. In this review, we emphasize on the role of bacterial cell cycle synchronization as one of the intrinsic mechanisms used by the bacteria to cope with stress response and perhaps involved in evolution of its drug resistance. The importance of cell cycle synchronization and its function in drug resistance in cancer cells, malarial and viral pathogens is well understood, but its role in bacterial pathogens has yet to be established. From the extensive literature survey, we could collect information regarding how mycobacteria use synchronization to overcome the stress response. Additionally, it has been observed that most of the microbial pathogens including mycobacteria are responsive to drugs predominantly in their logarithmic phase, while they show resistance to antibiotics when they are in the lag or stationary phase. Therefore, we speculate that Mtb might use this novel strategy wherein they regulate their cell cycle upon antibiotic pressure such that they either enter in their low metabolic phase i.e., either the lag or stationary phase to overcome the antibiotic pressure and function as persister cells. Thus, we propose that manipulating the mycobacterial drug resistance could be possible by fine-tuning its cell cycle.

Synergies in stem cell research: Integrating technologies, strategies, and bionanomaterial innovations.

Since the 1960 s, there has been a substantial amount of research directed towards investigating the biology of several types of stem cells, including embryonic stem cells, brain cells, and mesenchymal stem cells. In contemporary times, a wide array of stem cells has been utilized to treat several disorders, including bone marrow transplantation. In recent years, stem cell treatment has developed as a very promising and advanced field of scientific research. The progress of therapeutic methodologies has resulted in significant amounts of anticipation and expectation. Recently, there has been a notable proliferation of experimental methodologies aimed at isolating and developing stem cells, which have emerged concurrently. Stem cells possess significant vitality and exhibit vigorous proliferation, making them suitable candidates for in vitro modification. This article examines the progress made in stem cell isolation and explores several methodologies employed to promote the differentiation of stem cells. This study also explores the method of isolating bio-nanomaterials and discusses their viewpoint in the context of stem cell research. It also covers the potential for investigating stem cell applications in bioprinting and the usage of bionanomaterial in stem cell-related technologies and research. In conclusion, the review article concludes by highlighting the importance of incorporating state-of-the-art methods and technological breakthroughs into the future of stem cell research. Putting such an emphasis on constant innovation highlights the ever-changing character of science and the never-ending drive toward unlocking the maximum therapeutic potential of stem cells. This review would be a useful resource for researchers, clinicians, and policymakers in the stem cell research area, guiding the next steps in this fast-developing scientific concern.

Deciphering Target Protein Cascade in Salmonella typhi Biofilm using Genomic Data Mining, and Protein-protein Interaction.

Background: Salmonella typhi biofilm confers a serious public health issue for lengthy periods and the rise in antibiotic resistance and death rate. Biofilm generation has rendered even the most potent antibiotics ineffective in controlling the illness, and the S. typhi outbreak has turned into a fatal disease typhoid. S. typhi infection has also been connected to other deadly illnesses, such as a gall bladder cancer. The virulence of this disease is due to the interaction of numerous genes and proteins of S. typhi. Objective: The study aimed to identify a cascade of target proteins in S. typhi biofilm condition with the help of genomic data mining and protein-protein interaction analysis. Methods: The goal of this study was to notice some important pharmacological targets in S. typhi. using genomic data mining, and protein-protein interaction approaches were used so that new drugs could be developed to combat the disease. Results: In this study, we identified 15 potential target proteins that are critical for S. typhi biofilm growth and maturation. Three proteins, CsgD, AdrA, and BcsA, were deciphered with their significant role in the synthesis of cellulose, a critical component of biofilm's extracellular matrix. The CsgD protein was also shown to have high interconnectedness and strong interactions with other important target proteins of S. typhi. As a result, it has been concluded that CsgD is involved in a range of activities, including cellulose synthesis, bacterial pathogenicity, quorum sensing, and bacterial virulence. Conclusion: All identified targets in this study possess hydrophobic properties, and their cellular localization offered proof of a potent therapeutic target. Overall results of this study, drug target shortage in S. typhi is also spotlighted, and we believe that obtained result could be useful for the design and development of some potent anti-salmonella agents for typhoid fever in the future.

Paclitaxel Delivery to the Brain for Glioblastoma Treatment.

The development of paclitaxel-loaded polymeric nanoparticles for the treatment of brain tumors was investigated. Poly(lactide-glycolide) (PLGA) nanoparticles containing 10% w/w paclitaxel with a particle size of 216 nm were administered through intranasal and intravenous routes to male Sprague-Dawley rats at a dose of 5 mg/kg. Both routes of administration showed appreciable accumulation of paclitaxel in brain tissue, liver, and kidney without any sign of toxicity. The anti-proliferative effect of the nanoparticles on glioblastoma tumor cells was comparable to that of free paclitaxel.

Secondary metabolites from endophytic fungi: Production, methods of analysis, and diverse pharmaceutical potential.

The synthesis of secondary metabolites is a constantly functioning metabolic pathway in all living systems. Secondary metabolites can be broken down into numerous classes, including alkaloids, coumarins, flavonoids, lignans, saponins, terpenes, quinones, xanthones, and others. However, animals lack the routes of synthesis of these compounds, while plants, fungi, and bacteria all synthesize them. The primary function of bioactive metabolites (BM) synthesized from endophytic fungi (EF) is to make the host plants resistant to pathogens. EF is a group of fungal communities that colonize host tissues' intracellular or intercellular spaces. EF serves as a storehouse of the above-mentioned bioactive metabolites, providing beneficial effects to their hosts. BM of EF could be promising candidates for anti-cancer, anti-malarial, anti-tuberculosis, antiviral, anti-inflammatory, etc. because EF is regarded as an unexploited and untapped source of novel BM for effective drug candidates. Due to the emergence of drug resistance, there is an urgent need to search for new bioactive compounds that combat resistance. This article summarizes the production of BM from EF, high throughput methods for analysis, and their pharmaceutical application. The emphasis is on the diversity of metabolic products from EF, yield, method of purification/characterization, and various functions/activities of EF. Discussed information led to the development of new drugs and food additives that were more effective in the treatment of disease. This review shed light on the pharmacological potential of the fungal bioactive metabolites and emphasizes to exploit them in the future for therapeutic purposes.

Phospholipase C: underrated players in microbial infections.

During bacterial infections, one or more virulence factors are required to support the survival, growth, and colonization of the pathogen within the host, leading to the symptomatic characteristic of the disease. The outcome of bacterial infections is determined by several factors from both host as well as pathogen origin. Proteins and enzymes involved in cellular signaling are important players in determining the outcome of host-pathogen interactions. phospholipase C (PLCs) participate in cellular signaling and regulation by virtue of their ability to hydrolyze membrane phospholipids into di-acyl-glycerol (DAG) and inositol triphosphate (IP3), which further causes the activation of other signaling pathways involved in various processes, including immune response. A total of 13 PLC isoforms are known so far, differing in their structure, regulation, and tissue-specific distribution. Different PLC isoforms have been implicated in various diseases, including cancer and infectious diseases; however, their roles in infectious diseases are not clearly understood. Many studies have suggested the prominent roles of both host and pathogen-derived PLCs during infections. PLCs have also been shown to contribute towards disease pathogenesis and the onset of disease symptoms. In this review, we have discussed the contribution of PLCs as a determinant of the outcome of host-pathogen interaction and pathogenesis during bacterial infections of human importance.

Data on differential pathogenic ability of Helicobacter pylori isolated from distinct gastric niches.

Helicobacter pylori infection is associated with various gastrointestinal diseases and gastric cancer. Our data shows the H. pylori isolates and their associated pathology, isolated from two different stomach niches: gastric epithelium and gastric juice. Gastric adenocarcinoma (AGS) cells were infected with H. pylori juice (HJ1, HJ10 and HJ14) and biopsy (HB1, HB10 and HB14) isolates for 6, 12 and 24 hrs. To determine the cell migration ability of the infected cells, scratch wound assay was performed. The decrease in the wound area was measured by Image J software. Status of cell proliferation accessed by counting the cell number through trypan blue exclusion method. Further assessment of pathogenic potential and carcinogenic ability of the isolates was done by determining the genomic instability in the cell post infection. Cells were stained with DAPI and number of micro and macro nuclei was counted in the acquired images. The data will be helpful in understanding the difference in the carcinogenic ability of H. pylori with respect to their physiological niche.

Substantial relation between the bacterial biofilm and oncogenesis progression in host.

Globally, bacteria are well-known microorganisms for bacterial biofilm infection. Bacterial biofilm has generated antibiotic resistance and led the persistent infection. But new complications arise with a biofilm that bacterial biofilm shows the new association with oncogenesis. Some bacteria have a carcinogenic nature at the chronic infection stage like Salmonella Typhi, Helicobacter pylori. Thus, biofilm has a significant role in oncogenesis. Few pieces of evidence also support that the bacterial biofilm has a potential role to develop oncogenesis in the human body. Bacterial biofilm is responsible to induce chronic inflammation and is the main basis for the oncogenesis process. But bacterial biofilm association with the oncogenesis mechanism is unknown yet. This article focuses on the function of bacterial biofilm in tumor formation and the mechanism that encourages the oncogenesis and provide a possible and interesting hypothesis involved in between biofilm and host oncogenesis progression. The discussed relationship will provide a sound direction in the field of oncology and concept may give an informative direction in diagnosis and treatment. Bacterial biofilm behavior could be significantly linked with cancer cell formation. This article attracts the attention of researchers of the field because biofilm mediated oncogenesis further indicate towards an important issue in human health.

Resistance-proof antimicrobial drug discovery to combat global antimicrobial resistance threat.

Drug resistance is well-defined as a serious problem in our living world. To survive, microbes develop defense strategies against antimicrobial drugs. Drugs exhibit less or no effective results against microbes after the emergence of resistance because they are unable to cross the microbial membrane, in order to alter enzymatic systems, and/or upregulate efflux pumps, etc. Drug resistance issues can be addressed effectively if a "Resistance-Proof" or "Resistance-Resistant" antimicrobial agent is developed. This article discusses first the need for resistance-proof drugs, the imminent properties of resistance-proof drugs, current and future research progress in the discovery of resistance-proof antimicrobials, the inherent challenges, and opportunities. A molecule having imminent resistance-proof properties could target microbes efficiently, increase potency, and rule out the possibility of early resistance. This review triggers the scientific community to think about how an upsurge in drug resistance can be averted and emphasizes the discussion on the development of next-generation antimicrobials that will provide a novel effective solution to combat the global problem of drug resistance. Hence, resistance-proof drug development is not just a requirement but rather a compulsion in the drug discovery field so that resistance can be battled effectively. We discuss several properties of resistance-proof drugs which could initiate new ways of thinking about next-generation antimicrobials to resolve the drug resistance problem. This article sheds light on the issues of drug resistance and discusses solutions in terms of the resistance-proof properties of a molecule. In summary, the article is a foundation to break new ground in the development of resistance-proof therapeutics in the field of infection biology.

Biochemical aspects of effects of mesenchymal stem cell treatment in chronic wounds progressive healing.

Chronic wounds are a persistent burden for medical professionals. Despite developments and advancements in treatment, these wounds do not heal completely. Mesenchymal stem cells (MSCs) are the epicenter of regenerative medicine that have shown promising results in chronic wound regeneration. Autologous peripheral blood-derived MSCs (PB-MSCs) are comparatively new in wound healing treatment, bone-marrow-derived MSCs (BM-MSCs), and adipose-derived stem cells (ADSCs) are commonly being practiced. In the present study, PB-MSCs treatment was given to chronic wound patients. Various biochemical parameters like random blood glucose, serum urea, serum creatinine, bilirubin (total and direct), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), total protein, albumin levels, and association of other factors/conditions such as age, sex, addiction of drug/alcohol were also evaluated/compared with complete and without complete healing. The wound area of the ulcer was found to be significantly reduced and the wound was healthier after the treatment. These biochemical parameters could be certainly utilized as biomarkers to anticipate the risk of chronic wounds. These findings may contribute to the development of better wound care treatment strategies and drug discovery in the field of regenerative medicine.

Ayurveda and in silico Approach: A Challenging Proficient Confluence for Better Development of Effective Traditional Medicine Spotlighting Network Pharmacology.

Coalescence of traditional medicine Ayurveda and in silico technology is a rigor for supplementary development of future-ready effective traditional medicine. Ayurveda is a popular traditional medicine in South Asia, emanating worldwide for the treatment of metabolic disorders and chronic illness. Techniques of in silico biology are not much explored for the investigation of a variety of bioactive phytochemicals of Ayurvedic herbs. Drug repurposing, reverse pharmacology, and polypharmacology in Ayurveda are areas in silico explorations that are needed to understand the rich repertoire of herbs, minerals, herbo-minerals, and assorted Ayurvedic formulations. This review emphasizes exploring the concept of Ayurveda with in silico approaches and the need for Ayurinformatics studies. It also provides an overview of in silico studies done on phytoconstituents of some important Ayurvedic plants, the utility of in silico studies in Ayurvedic phytoconstituents/formulations, limitations/challenges, and prospects of in silico studies in Ayurveda. This article discusses the convergence of in silico work, especially in the least explored field of Ayurveda. The focused coalesce of these two domains could present a predictive combinatorial platform to enhance translational research magnitude. In nutshell, it could provide new insight into an Ayurvedic drug discovery involving an in silico approach that could not only alleviate the process of traditional medicine research but also enhance its effectiveness in addressing health care.

Fabrication and analysis of chitosan oligosaccharide based mucoadhesive patch for oromucosal drug delivery.

OBJECTIVE: Fabrication and analyses of mucoadhesive patches made from chitosan oligosaccharide for the purpose of oromucosal drug delivery. SIGNIFICANCE: The mucosal epithelium in the oral cavity, consisting of buccal and sublingual epithelium, has gained significant attention in the last decade as an alternative anatomical site for systemic drug delivery that could potentially minimize the challenges of solid oral dosage and parenteral delivery. In this study, we have fabricated and tested drug-loaded chitosan oligosaccharide-based patches for the oromucosal drug delivery. METHODS: The chitosan oligosaccharide (with and without alginate) based patches were fabricated using the conventional solvent casting method and were analyzed for their swelling capacity, hydrophilicity, anti-cancer activity, in vitro drug release, and in vivo drug release activity. The in-house developed artificial saliva was used for the swelling study. RESULTS: Alginate-containing patches showed lesser swelling ability compared to the bare chitosan oligosaccharide-based patches. The former was also found to be more hydrophobic compared to the latter one. Both the unloaded patches restricted the growth of epithelial cancer cells indicating their anti-cancer behavior. In vitro drug release indicated a super case II release pattern while in vivo study demonstrated the release of drug from the patch into the plasma indicating the purpose of the fabricated patch. CONCLUSIONS: The chitosan oligosaccharide-based mucoadhesive hydrogel patch fabricated in this study can be highly suitable for possible translational purposes.

Initial Retrocolic Endoscopic Tunnel Approach As an Ergonomic and Oncologically Apt Laparoscopic Technique for Resection of Malignant Right Colonic Lesions: An Experience from a University Hospital.

Introduction: Radical minimal access cancer surgery has demonstrated similar outcomes as open surgery of late, but with less morbidity, improving the quality of life especially in patients with colorectal cancer. Initial retrocolic endoscopic tunnel approach (IRETA) has been described in the literature by Palanivelu et al. as a laparoscopic technique for radical resection of malignant right colonic lesions (MRCL) following the modified concept of medial to lateral dissection. In this work, the authors present their experience of this ergonomic surgical technique. Materials and Methods: To begin with, retrocolic dissection was carried out to free and dissect the ascending colon up to hepatic flexure with the reflection of the peritoneum over the right colon along the white line of Toldt with abdominal wall kept intact initially to sustain intracorporeal specimen steadiness. Subsequently, the specimen is lifted medially in a distinct lymphovascular sheath, leading to high ligation of ileocolic, right colic, and the right branch of the middle colic vein with a consequent definite en bloc thorough removal of the lesion. The specimen was delivered through a transumbilical incision. Results: Ten patients (age 45.4 ± 5.6 years) underwent resection by the IRETA technique with a mean operating time of 185 ± 30 minutes and blood loss of 90 ± 20 mL. Mean hospital stay was 6 days. R0 surgical resection was achieved in all patients with proper marginal clearance. Ninety percent had adequate lymph nodal resection. One patient had an intraoperative complication and n = 3 patients developed postoperative ileus. Adjuvant chemotherapy was given and there is no recurrence on 28 months of average follow-up. Conclusion: With the increasing use of laparoscopic surgery for the management of colorectal cancers, the IRETA technique appears to be an ergonomic and oncologically robust procedure for the removal of MRCL. The presented data set needs to be increased with at least 5 years of follow-up to establish long-term surgical outcomes.

Characterization and Evaluation of Injectable Biodegradable Polymer Multimodality Radiologic Markers in an In Vivo Murine Model.

Biodegradable polymer clips as multidimensional soft tissue biopsy markers were developed with better biocompatibility and imaging features. Unlike the commercially available metallic biopsy markers, the developed polymer clips are temporary implants with similar efficacies as metal markers in imaging and detection and get absorbed within the body with time. Herein, we evaluate the degradation rate of three resorbable polymer-based marker compounds in an in vivo murine model. Three polymers, abbreviated as Polymer A (PLGA poly(lactic-co-glycolic acid)50:50), Polymer B (PLGA (poly(lactic-co-glycolic acid)) 75:25), and Polymer C (polycaprolactone (PCL)), mixed with 20% lipiodol and 0.2% iron oxide and a control polymer were implanted into nine mice, followed by CT and MRI imaging. Images were evaluated for conspicuity. Specimens were examined for tissue analysis of iodine and iron contents. Significant differences in polymer resorption and visualization on CT were noted, particularly at 8 weeks (p < 0.027). Polymers A, B, and C were visible by CT at 4, 6, and 8 weeks, respectively. All marker locations were detected on MRI (T1 and SWI) after 24 weeks, with tattooing of the surrounding soft tissue by iron deposits. CT and MR visible polymer markers can be constructed to possess variable resorption, with stability ranging between 4 and 14 weeks post placement, making this approach suitable for distinct clinical scenarios with varying time points.

l-asparaginase: Need for an Expedition from an Enzymatic Molecule to Antimicrobial Drug.

Enzymes play a vital role in the biological system as a catalyst for biochemical reactions. They have a wide range of commercial applications in many areas like the pharmaceutical industry, food industry, etc. l-asparaginase is one of the commercial enzymes with prime importance in anticancer therapy. It is mainly used in chemotherapy; however, it has the potential to cure autoimmune disorders and infectious diseases also. Previous studies reported the antimicrobial potential of l-asparaginase. Therefore, we have discussed the possibility and challenges of the antimicrobial application of l-asparaginase in the treatment of infectious diseases. This is followed by a discussion on the effective delivery of this enzyme using biopolymeric nanocarriers that ensure safe and on target action. The present article gives a perspective on the l-asparaginase molecule that could be developed/established as an approved antimicrobial drug in the future.

Proteasome Based Molecular Strategies Against Improper Cellular Proliferation.

Cells contain several proteins that routinely fulfill multiple requirements for normal physiological survival. Proteostasis dysfunction is linked with different complex human disorders, like cancer, neuron degeneration, and imperfect aging. The ubiquitin proteasome system (UPS) forms the primary proteostasis mechanism taking part in cytoprotection. Cancer cells are well known to possess enhanced cytoprotective properties, and different UPS elements are implicated to be dysregulated at several stages of tumor progression. Furthermore, many studies have found tumor cells to exhibit higher levels of various UPS components, possibly contributing to their robust endurance. In this article, we have presented different cellular protein quality control strategies, essential for maintaining healthy proteome. Here, we have also discussed key contributions and functions of UPS involved in molecular pathomechanisms for establishing cancer conditions. Along with this, the emerging different therapeutic strategies against defective proteome linked with improper cellular proliferation and cancer progression are also reviewed. UPS performs critical regulatory functions in modulating the cellular apoptotic pathways. The proteasomal system involvement as probable therapeutic targets influencing cancer cell apoptosis is also discussed. Our article summarizes the recent developments in proteasome-associated pathways regulating tumor cell proteome and survival. Additionally, how the engagement and cross functions of these physiological processes can induce apoptosis and may develop regulation over tumor progression. A better understanding of multifaceted protein quality control pathways may inform therapeutic interventions based on cellular proteostasis response determined against complex diseases.

A prospective randomised control trial to compare the perioperative outcomes and ergonomic challenges between triangular versus midline port placement in total extra-peritoneal repair of uncomplicated unilateral inguinal hernia.

BACKGROUND: Routine TEP technique requires three skin incisions for placement of three trocars in the midline. Otherwise, this can be done by three-port triangular technique or two-hand technique. This study reports a randomised trial of perioperative outcomes and ergonomics characteristics of this procedure using two different techniques of port insertion. METHODS: N = 28 patients were randomised into two groups for triangular three-port (TTEP) versus midline three-port TEP (MTEP) hernioplasty after informed written consent in Department of Surgery, King George's Medical University UP between September 2016 and September 2017 after institutional ethical approval. Patient-related outcomes in terms of quality of life (QOL) and ergonomic evaluation of the technique were compared in double-blinded fashion. RESULTS: Postoperative pain score at 24 h post surgery (5.1 ± 0.6; 95% CI 4.9-5.3 vs. 4.8 ± 0.4; 95% CI 4.6-4.9) differed, while hospital stay, time to return to routine work, tolerance to oral feeds and intraoperative complications occurrence (OR 2.1; 95% CI 0.2-24.3) were comparable in both groups. Time to return to office work (5.5 ± 0.5; 95% CI 5.4-5.7 vs. 4.0 ± 0.8; 95% CI 3.7-4.3) and immediate postoperative sensation of mesh and pain score were significantly higher in MTEP compared to TTEP. Ergonomic parameters including visualization of landmark score, spreading of mesh score and total surgeon satisfaction score (TTEP 8.4 ± 0.7; 95% CI 8.1-8.6 vs. MTEP 7.0 ± 0.8; 95% CI 6.7-7.3), mental effort quotient (SMEQ score: TTEP 50.6 ± 12.7; 95% CI 45.9-55.3 vs. MTEP 70.8 ± 12.6: 95% CI 66.1-75.4) and physical effort quotient (LEDQ scores in wrist, hand, arm and shoulders) were also superior in triangular technique of port placement. CONCLUSION: Triangular three-port TEP hernioplasty is ergonomically feasible and enables a surgeon to perform surgery safely using basic principles of laparoscopy.

Role of nano-selenium in health and environment.

In recent years, researches on selenium nanoparticle have gained more attention due to its important role in many physiological processes. Generally, selenium nanoparticle has a high level of absorption in regular supplementation comparative to selenium. Therefore it is all-important to develop new techniques to elevate the transportation of selenium compounds (selenoproteins, selenoenzymes, etc.) by increasing their bioavailability, bioactivity, and controlled release. SeNPs have special attention regarding their application as food additives and therapeutic agents. Selenium nanoparticle has biomedical and pharmaceutical uses due to its antioxidant, antimicrobial, antidiabetic, and anticancer effects. Selenium nanoparticle is also used to antagonize the toxic effect of chemical and heavy metals. SeNPs are beneficial for the treatment of water and soil contaminated with metals and heavy metals as it has adsorption capability. Selenium nanoparticle is synthesized by the bioreduction of selenium species (sodium selenate, sodium selenite, selenium dioxide, and selenium tetrachloride, etc.) by using bacteria, fungi, plant, and plant extracts, which have given hope for the bioremediation of selenium contaminated water and soils. This article reviews the procedure of selenium nanoparticle synthesis (physical, chemical and biological methods), characterization (UV-vis spectroscopy, transmission electron microscopy, Scanning electron microscopy, electron dispersive X-ray spectroscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, etc.), with the emphasis on its role and application in health and environment.

Host phospholipase C-γ1 impairs phagocytosis and killing of mycobacteria by J774A.1 murine macrophages.

Macrophages represent the first line of defense against invading Mycobacterium tuberculosis (Mtb). In order to enhance intracellular survival, Mtb targets various components of the host signaling pathways to limit macrophage functions. The outcome of Mtb infection depends on various factors derived from both host and pathogen. A detailed understanding of such factors operating during interaction of the pathogen with the host is a prerequisite for designing new approaches for combating mycobacterial infections. This work analyzed the role of host phospholipase C-γ1 (PLC-γ1) in regulating mycobacterial uptake and killing by J774A.1 murine macrophages. Small interfering RNA mediated knockdown of PLC-γ1 increased internalization and reduced the intracellular survival of both Mtb and Mycobacterium smegmatis (MS) by macrophages. Down-regulation of the host PLC-γ1 was observed during the course of mycobacterial infection within these macrophages. Finally, Mtb infection also suppressed the expression of pro-inflammatory cytokine tumor necrosis factor-α and chemokine (C-C motif) ligand 5 (RANTES) which was restored by knocking down PLC-γ1 in J774A.1 cells. These observations suggest a role of host PLC-γ1 in the uptake and killing of mycobacteria by murine macrophages.