Comprehensive study of the interplay between immunological and metabolic factors in hepatic steatosis.

The pathophysiology of hepatic steatosis is thoroughly reviewed in this comprehensive report, with particular attention to the complex interactions between inflammatory pathways, insulin resistance, lipid metabolism, metabolic dysregulation, and immunological responses in the liver including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). The study highlights the role of immune cell regulation in disease progression and explores the potential of immune cell-specific treatments for treating hepatic disorders. The development of liver disorders is significantly influenced by immune cells, including dendritic cells, T cells, and natural killer cells. Clinical investigations show that immune cell-specific treatments can effectively reduce liver fibrosis and inflammation. Future research should focus on finding new immunological targets for therapeutic interventions, as well as addressing the management challenges associated with NAFLD/NASH. Hepatic immune microorganisms also impact liver homeostasis and disorders. Improvements in immune cell regulation and liver transplantation methods give patients hope for better prognoses. Important phases include optimizing the selection of donors for malignancy of the liver, using machine perfusion for organ preservation, and fine-tuning immunosuppressive strategies. For focused treatments in hepatic steatosis, it is imperative to understand the intricate interactions between immune and metabolic variables. Understanding the liver's heterogeneous immune profile, encompassing a range of immune cell subpopulations, is crucial for formulating focused therapeutic interventions. To improve patient care and outcomes in hepatic illnesses, there is an urgent need for further research and innovation. Therefore, to effectively treat hepatic steatosis, it is important to enhance therapeutic techniques and maximize liver transplantation strategies.

Quercetin inhibits NF-kB and JAK/STAT signaling via modulating TLR in thymocytes and splenocytes during MSG-induced immunotoxicity: an in vitro approach.

BACKGROUND: The most widely used food additive monosodium glutamate (MSG) has been linked to immunopathology. Conversely, quercetin (Q), a naturally occurring flavonoid has been demonstrated to have immunomodulatory functions. Therefore, the purpose of the study is to determine if quercetin can mitigate the deleterious effects of MSG on immune cells, and the possible involvement of TLR, if any.  METHODS AND RESULTS: This study was conducted on Q, to determine how it affects the inflammatory response triggered by MSG in primary cultured thymocytes and splenocytes from rats (n = 5). Q shielded cells by augmenting cell survival and decreasing lactate dehydrogenase leakage during MSG treatment. It decreased IL-1ß, IL-6, IL-8, and TNF-α expression and release by hindering NF-kB activation and by inhibiting the JAK/STAT pathway. Moreover, Q prevented NLRP3 activation, lowered IL-1ß production, and promoted an anti-inflammatory response by increasing IL-10 production. Q reduced MSG-induced cellular stress and inflammation by acting as an agonist for PPAR-γ and LXRα, preventing NF-kB activation, and lowering MMP-9 production via increasing TIMP-1. Additionally, Q neutralized free radicals, elevated intracellular antioxidants, and impeded RIPK3, which is involved in inflammation induced by oxidative stress, TNF-α, and TLR agonists in MSG-treated cells. Furthermore, it also modulated TYK2 and the JAK/STAT pathway, which exhibited an anti-inflammatory effect. CONCLUSIONS: MSG exposure is associated with immune cell dysfunction, inflammation, and oxidative stress, and Q modulates TLR to inhibit NF-kB and JAK/STAT pathways, providing therapeutic potential. Further research is warranted to understand Q's downstream effects and explore its potential clinical applications in inflammation.

Quercetin counteracts monosodium glutamate to mitigate immunosuppression in the thymus and spleen via redox-guided cellular signaling.

BACKGROUND: Chronic inflammation brought on by oxidative stress can result in several immunopathologies. Natural compounds with antioxidant characteristics, like quercetin, have shown effectiveness in reducing oxidative damage and regulating the immune response. PURPOSE: The commonly used food additive monosodium glutamate (M) causes immunosuppression by disrupting redox equilibrium and inducing oxidative stress. The goal of this work is to examine the therapeutic potential of quercetin against immunotoxicity brought on by M, revealing the molecular route implicated in such immunopathology by targeting the thymus and spleen, to support the development of future anti-inflammatory and antioxidant therapies. STUDY DESIGN AND METHODS: M-fed rats were employed as an immunotoxicity model and were supplemented with quercetin for four weeks. Hematological and biochemical parameters were measured; H&E staining, immunohistochemistry, flow cytometry, real-time quantitative PCR, and western blotting were performed. RESULTS: Based on the findings, TLR4 was activated by M to cause oxidative stress-mediated inflammation, which was alleviated by the supplementation of quercetin by modulating redox homeostasis to neutralize free radicals and suppress the inflammatory response. To prevent M-induced inflammation, quercetin demonstrated anti-inflammatory functions by blocking NF-kB activation, lowering the production of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines. By normalizing lipid profiles and lowering the potential risk of immunological deficiency caused by M, quercetin also improves lipid metabolism. Additionally, it has shown potential for modifying insulin levels, suggesting a possible function in controlling M-induced alteration in glucose metabolism. The addition of quercetin to M enhanced the immune response by improving immunoglobulin levels and CD4/CD8 expression in the thymus and spleen. Additionally, quercetin inhibited apoptosis by controlling mitochondrial caspase-mediated cellular signaling, suggesting that it may be able to halt cell death in M-fed rats. CONCLUSION: The results of this study first indicate that quercetin, via modulating redox-guided cellular signaling, has a promising role in reducing immune disturbances. This study illuminates the potential of quercetin as a safe, natural remedy for immunopathology caused by M, including thymic hypoplasia and/or splenomegaly, and paves the way for future anti-inflammatory and antioxidant supplements.

Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development.

The discovery and advances of medicines may be considered as the ultimate relevant translational science effort that adds to human invulnerability and happiness. But advancing a fresh medication is a quite convoluted, costly, and protracted operation, normally costing USD ~2.6 billion and consuming a mean time span of 12 years. Methods to cut back expenditure and hasten new drug discovery have prompted an arduous and compelling brainstorming exercise in the pharmaceutical industry. The engagement of Artificial Intelligence (AI), including the deep-learning (DL) component in particular, has been facilitated by the employment of classified big data, in concert with strikingly reinforced computing prowess and cloud storage, across all fields. AI has energized computer-facilitated drug discovery. An unrestricted espousing of machine learning (ML), especially DL, in many scientific specialties, and the technological refinements in computing hardware and software, in concert with various aspects of the problem, sustain this progress. ML algorithms have been extensively engaged for computer-facilitated drug discovery. DL methods, such as artificial neural networks (ANNs) comprising multiple buried processing layers, have of late seen a resurgence due to their capability to power automatic attribute elicitations from the input data, coupled with their ability to obtain nonlinear input-output pertinencies. Such features of DL methods augment classical ML techniques which bank on human-contrived molecular descriptors. A major part of the early reluctance concerning utility of AI in pharmaceutical discovery has begun to melt, thereby advancing medicinal chemistry. AI, along with modern experimental technical knowledge, is anticipated to invigorate the quest for new and improved pharmaceuticals in an expeditious, economical, and increasingly compelling manner. DL-facilitated methods have just initiated kickstarting for some integral issues in drug discovery. Many technological advances, such as "message-passing paradigms", "spatial-symmetry-preserving networks", "hybrid de novo design", and other ingenious ML exemplars, will definitely come to be pervasively widespread and help dissect many of the biggest, and most intriguing inquiries. Open data allocation and model augmentation will exert a decisive hold during the progress of drug discovery employing AI. This review will address the impending utilizations of AI to refine and bolster the drug discovery operation.

An Outlook Towards Nano-Sponges: A Unique Drug Delivery System and its Application in Drug Delivery.

Nanosponges are colloidal and crosslinked nanocarriers consisting of a solid mesh-like network with nanocavities to encompass various types of substances like antineoplastic, proteins, peptides, volatile oil, DNA and then incorporated into topical medications that are mainly formulated such as gels, creams, lotions, ointments, liquid and powders etc. for topical drug delivery system. In the polymeric construction of nanosponges, the release of enthalpy-rich water molecules accounts for high complexation efficiency for different molecular substances. The benefits of nanosponges involve the extended and controlled release of encapsulated particles with excellent competence and great stability. Nanosponges assume a significant part in new varieties of medicaments, beautifiers, farming, horticulture, high atomic weight containing proteins, innovative fire retardants, gas transporters, and water filters. Nanosponges are a novel technology that offers controlled and targeted drug delivery by various routes like oral, parenteral, and topical routes. Nanosponges are an effective transporter for biologically active ingredients; therefore, it is broadly employed in anti-cancer, antiviral, antiplatelet, and antilipidemic therapy. This review article gives attention to the general introduction, merits and demerits, classification, characteristic features, procedures for developing nanosponges, and numerous factors which affect nanosponge formulation, evaluation parameters, and applications in the medicinal industry.

Synthesis of Biogenic Hematite Nanocubes as Recyclable Dark Fenton-like Catalysts at Neutral pH and Plant Growth Applications of Degraded Waste Water.

The goal of this study is to fabricate bioinspired metal oxide nanocubes from lemon peel extract in an environmentally friendly manner and evaluate its impact on environmental remediation. In neutral pH, the degradation kinetics of methylene blue dye (MB) in the aqueous phase was investigated using iron oxide nanoparticles as a catalyst. The obtained results revealed that under optimum conditions, synthesized Fe2O3 nanoparticles (IONPs) offered ultrafast dark Fenton-like reaction to degrade MB. The size, morphological structures, and stability were confirmed through dynamic light scattering, field emission scanning electron microscopy, X-ray diffraction, and ζ potential analysis. The overall environmental impact of the process was assessed by growing wheat plants with treated wastewater and evaluating their biochemical attributes. Antibacterial activity was investigated against Gram-positive (Bacillus megaterium, Bacillus subtilis) and Gram-negative (Escherichia coli, Salmonella typhimurium) aerobics and Gram-positive cocci (Staphylococcus aureus). The antifungal activity was measured against Fusarium solani by spore germination inhibition and zone inhibition of fungal pathogens for different nanocube concentrations.

Effects of plant growth retardant daminozide (Alar) on neuromuscular co-ordination behavior in Drosophila melanogaster.

Daminozide (alar), a plant growth retardant, is used in different fruit orchard to make fruits attractive and reduce pre-harvest losses. Previously data demonstrated that acute daminozide exposure affected reproductive fitness and produced neurodegeneration in Drosophila melanogaster. The goal of this study was to determine whether continuous exposure to daminozide affects neuromuscular co-ordination in D. melanogaster as manifested in various behavioral responses. Fruit flies were exposed to 200 or 400 mg/L concentration of daminozide for two successive generations. Treated D. melanogaster were examined for the behaviors indicative of neuromuscular coordination and cognitive abilities, that include climbing, social interaction, adult grooming, migration, flight, male aggression, and adult courtship. Aberrant behavioral responses were noted among treated D. melanogaster of both sexes as evidenced by the following parameters: reduction in flight duration, abnormal social interaction, altered copulatory acts, and over-aggressiveness. Data suggest that daminozide produces impairment in neuromuscular coordination and cognitive ability in Drosophila, which was reflected as altered behavioral patterns. As Drosophila is considered as a reliable in vivo model utilized in toxicity testing, our findings may help us to anticipate and monitor potential daminozide-induced toxicity in animals and humans.

Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model.

Globally, the trend of using food additives and eating ready-made fast food has led to a deleterious impact on immune organs. Monosodium glutamate (MSG), as a food additive in a high-lipid diet (HLD), acts as a silent killer of immune cells. Hence, the present study aimed to evaluate the role of MSG in HLD on spleen injury in rats. Results showed that a 2.52-fold and 1.91-fold increase in spleen index in MSG and MSG + HLD group indicates splenomegaly, whereas a 1.36-fold and 1.29-fold increase in pro-inflammatory cytokines in MSG and MSG + HLD-fed rats, respectively, promote the inflammatory response. Additionally, MSG and MSG + HLD induce oxidative stress by 1.81-fold and 1.1-fold increased generation of reactive oxygen species (ROS) in macrophage population, and 1.38-fold and 1.36-fold increased generation of ROS in lymphocytes population, respectively. Furthermore, mitochondrial membrane potential was significantly reduced by 1.43-fold and 1.18-fold in MSG and MSG + HLD groups. Therefore, the current study argues that MSG has more detrimental effects on the spleen than MSG + HLD due to the presence of antioxidants in HLD, which suppresses the deleterious impact of MSG. Hence, it can be inferred that MSG induces spleen injury via targeting redox-guided cellular signaling with inflammatory response, leading to severe immune system anomalies.

Evaluation of potency of the selected bioactive molecules from Indian medicinal plants with MPro of SARS-CoV-2 through in silico analysis.

BACKGROUND: The recent outbreak of the novel SARS-CoV-2 across the globe and the absence of specific drug against this virus lead the scientific community to look into some alternative indigenous treatments. India as a hub of Ayurvedic and medicinal plants can shed light on its treatment using specific active bio-molecules from these plants. OBJECTIVES: Keeping our herbal resources in mind, we were interested to inquire whether some phytochemicals from Indian spices and medicinal plants can be used as alternative therapeutic agents in contrast to synthetic drugs. MATERIALS AND METHODS: We used in silico molecular docking approach to test whether bioactive molecules of herbal origin such as hyperoside, nimbaflavone, ursolic acid, 6-gingerol, 6-shogaol and 6-paradol, curcumin, catechins and epigallocatechin, α-Hederin, piperine could bind and potentially block the Mproenzyme of the SARS-CoV-2 virus. RESULTS: Ursolic acid showed the highest docking score (-8.7 kcal/mol) followed by hyperoside (-8.6 kcal/mol), α-Hederin (-8.5 kcal/mol) and nimbaflavone (-8.0 kcal/mol). epigallocatechin, catechins, and curcumin also exhibited high binding affinity (Docking score -7.3, -7.1 and -7.1 kcal/mol) with the Mpro. The remaining tested phytochemicals exhibited moderate binding and inhibitory effects. CONCLUSION: This finding provides a basis for biochemical assay of tested bioactive molecules on SARS-CoV-2 virus.

Childhood dental fear in children aged 7-11 years old by using the Children's Fear Survey Schedule-Dental Subscale.

In children, dental fear is not only associated with fear of pain or invasive procedures, but it is also correlated with separation from parents or confronting unfamiliar people or environments. The Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) was developed to evaluate dental fear in children, and this scale is now used across the world for evaluating dental fear. The aim of this study was to evaluate dental fear in children between 7-11 years of age and to find out the association between caries and fear of dental treatment. A total of 300 subjects of both sexes were enrolled in the study. Prior to the oral examination, all patients' attendants were informed about the study, and the subjects were asked to fill in a questionnaire regarding the CFSS-DS scale. The data obtained through the questionnaires were analyzed using the Chi-Square test. Fear scores were highest for "injections" (3.91±0.17), "dentist drilling" (3.91±0.10) and "choking" (3.65±0.82). It was also observed that subjects who had already visited a dental clinic or those who were familiar with the dental environment at an early stage of life were less anxious than patients who were receiving dental treatment for the first time. In this study, we found that female subjects were more anxious in comparison to male patients. Once the child's fear is identified, the dentist can use various behavior modification techniques to eliminate fear, explain the steps, and use the instruments accordingly until fear has vanished.

A rapid review of recent advances in diagnosis, treatment and vaccination for COVID-19.

COVID-19 is caused by SARS-CoV-2, which originated in Wuhan, Hubei province, Central China, in December 2019 and since then has spread rapidly, resulting in a severe pandemic. The infected patient presents with varying non-specific symptoms requiring an accurate and rapid diagnostic tool to detect SARS-CoV-2. This is followed by effective patient isolation and early treatment initiation ranging from supportive therapy to specific drugs such as corticosteroids, antiviral agents, antibiotics, and the recently introduced convalescent plasma. The development of an efficient vaccine has been an on-going challenge by various nations and research companies. A literature search was conducted in early December 2020 in all the major databases such as Medline/PubMed, Web of Science, Scopus and Google Scholar search engines. The findings are discussed in three main thematic areas namely diagnostic approaches, therapeutic options, and potential vaccines in various phases of development. Therefore, an effective and economical vaccine remains the only retort to combat COVID-19 successfully to save millions of lives during this pandemic. However, there is a great scope for further research in discovering cost-effective and safer therapeutics, vaccines and strategies to ensure equitable access to COVID-19 prevention and treatment services.

Vancomycin-Induced Changes in Host Immunity and Behavior: Comparative Genomic and Metagenomic Analysis in C57BL/6 and BALB/c Mice.

BACKGROUND: The consequence of treatment with antibiotics on the gut microbiota can be destructive. The antibiotics, however, can be utilized to understand the role of gut microbiota on the host physiology. AIM: Earlier, we reported the efficacy of vancomycin in gut microbiota perturbation. We continued to understand the effect of restoration kinetics of perturbed gut microbiota on the immunity and behavior of Th1 (C57BL/6)- and Th2 (BALB/c)-biased mice. METHODS: We studied restoration kinetics of the gut microbiota for two months following the withdrawal of vancomycin treatment in both mice strains. We analyzed cecal microbiome composition, different behavioral assays, and expression of select genes associated with stress and barrier function in gut and brain. RESULTS: Metagenomic analysis of gut microbiota revealed that the treatment with vancomycin caused a significant decrease in the relative abundance of Firmicutes and Bacteroidetes phyla with a time-dependent increase in Proteobacteria and Verrucomicrobia phyla. Maximum restoration (> 70%) of gut microbiota happened by the 15th day of withdrawal of vancomycin. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice. We established the correlation patterns of gut microbiota alteration and its effect on (a) the behavior of mice, (b) expression of key brain molecules, and (c) immunity-related genes. CONCLUSIONS: The results revealed that the gut microbiome profiling, behavior, and immune responses varied significantly between Th1- and Th2-biased mice. By withdrawing the treatment with vancomycin of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal (untreated control) level.

Genes regulating development and behavior exhibited altered expression in Drosophila melanogaster exposed to bisphenol A: use of real-time quantitative PCR (qRT-PCR) and droplet digital PCR (ddPCR) in genotoxicity study.

Toxicity of bisphenol A on morphological and life-history traits of model insect Drosophila melanogaster was reported in our previous work. In the present study, we have analyzed the adversity of bisphenol A on the reproductive behavior of adult and on the expression of selected genes in the larva and adult stage of fruit fly exposed to bisphenol A (0.007 g/2 ml. or 3.5 mg/ml), in addition to determination of LC50 value of bisphenol A in larva and pupal stage. We employed both the quantitative reverse transcriptase PCR and droplet digital PCR for analyzing the expression profile of seven genes namely, decapentaplegic, vestigial, wingless, foraging, insulin-like receptor, doublesex, and fruitless. We found bisphenol A has more adverse effects on male sexual behavior than females. Moreover, we observed significant downregulation of all the selected genes in treated larvae except, fruitless in male where it showed significant upregulation. On contrary among the treated adult flies, significant downregulation of all target genes in both sexes is evident, except, doublesex and fruitless in males which showed significant upregulation. We did not observe any deviation of male: female sex ratio from 1:1 under bisphenol A exposure. All these results suggest bisphenol A adversely affects the optimum functioning of genes which are involved in the regulation of metabolic pathways, behavioral pattern, stress response, endocrine homeostasis, neural functioning, and the development of the specific organ in Drosophila melanogaster. Our result not only provides a foundation to study further the bisphenol A toxicity on different pivotal genes in Drosophila but also suggests the use of the droplet digital PCR technology in toxicity measurement at the molecular level in eukaryotic model systems.

Influence of Periodontal Infection as a Possible Risk Factor for Preterm Low Birth Weight.

BACKGROUND: There is emerging interest and increasing amount of evidence that support the interrelationship between periodontitis and systemic conditions. Epidemiological and microbiological-immunological studies have lent credence to the concept that periodontal disease may be a separate risk factor for cardiovascular disease, cerebrovascular disease, and respiratory disease, as well as preterm delivery of low-birth-weight infants. AIM: The aim of this study was to evaluate the influence of periodontal infection as a possible risk factor for preterm low birth weight (LBW) based on age, literacy, and hemoglobin level of mother. MATERIALS AND METHODS: The observational study was conducted on 200 subjects, which were selected from the free labor ward, District Hospital, Saifai, Etawah, UP, India. Periodontal examinations were performed using the World Health Organization criteria. The periodontal status of the mother was recorded using Community Periodontal Index. RESULTS: For this study, chi-square test was performed to know the effect of variables and to find out the statistical significance of the study. Age of mother shows statistical insignificant association with periodontal disease, whereas literacy of mothers showed statistical significant association with periodontal disease, and periodontal status and hemoglobin levels of the mothers also showed a significant association. CONCLUSION: The prevalence of LBW infants was considerably less in mothers with a healthy periodontium and increased with progressive periodontal disease.

Malignant Melanoma: A Double Malignancy or Second Malignant Neoplasm in a Patient of Acute Lymphoblastic Leukemia Following Therapy with a Composite Karyotype.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy of lymphoid origin seen with a peak incidence between 2 and 5 years. New drug regimen has increased the cure rate, although the risk of developing a second malignancy still persists. The common second malignant neoplasms in survivors of childhood ALL are hematolymphoid malignancies, central nervous system tumors, carcinomas, sarcomas, and bone tumors with a median latency of at least 10 years. There are also examples of nonmelanotic skin tumors such as basal cell carcinoma following ALL chemotherapy, but malignant melanoma is an extremely uncommon malignancy encountered. Melanoma is associated with genetic mutations such as CDKN2A, and CDK4 with an increased prevalence of second malignancy such as the lung, pancreas, and breast. However, double malignancy of melanoma with ALL is rare. Here, we report a rare case of malignant melanoma following ALL therapy associated with composite karyotype and early relapse.

Mechanistic study of attenuation of monosodium glutamate mixed high lipid diet induced systemic damage in rats by Coccinia grandis.

In the context of failure of treatment for non alcoholic fatty liver disease (NAFLD)-mediated systemic damages, recognition of novel and successful characteristic drug to combat these anomalous situations is earnestly required. The present study is aimed to evaluate protective value of ethanol extract of Coccinia grandis leaves (EECGL), naturally occurring medicinal plant, on NAFLD-mediated systemic damage induced by high lipid diet along with monosodium glutamate (HM)-fed rats. Our study uncovered that EECGL significantly ameliorates HM-induced hyperlipidemia, increased lipogenesis and metabolic disturbances (via up regulation of PPAR-α and PPAR-γ), oxidative stress (via reducing the generation of reactive oxygen species and regulating the redox-homeostasis) and inflammatory response (via regulating the pro-inflammatory and anti-inflammatory factors with concomitant down regulation of NF-kB, iNOS, TNF-α and up regulation of eNOS). Furthermore, EECGL significantly inhibited HM-induced increased population of cells in sub G0/G1 phase, decreased Bcl2 expression and thereby loss of mitochondrial membrane potential with over expression of Bax, p53, p21, activation of caspase 3 and 9 indicated the apoptosis and suppression of cell survival. It is perhaps the first comprehensive study with a mechanistic approach which provides a strong unique strategy for the management of HM-induced systemic damage with effective dose of EECGL.

Altered composition of high-lipid diet may generate reactive oxygen species by disturbing the balance of antioxidant and free radicals.

Background In the present era, obesity is increasing rapidly, and high dietary intake of lipid could be a noteworthy risk factor for the occasion of obesity, as well as nonalcoholic fatty liver disease, which is the independent risk factor for type 2 diabetes and cardiovascular disease. For a long time, high-lipid diet (HLD) in "fast food" is turning into part of our everyday life. So, we were interested in fulfilling the paucity of studies by means of preliminary evaluation of these three alternative doses of HLD on a rat model and elucidating the possible mechanism of these effects and divulging the most alarming dose. Methods Thirty-two rats were taken, and of these, 24 were fed with HLD in three distinctive compositions of edible coconut oil and vanaspati ghee in a ratio of 2:3, 3:2 and 1:1 (n = 8), orally through gavage at a dose of 10 mL/kg body weight for a period of 28 days, whereas the other eight were selected to comprise the control group. Results After completion of the experiment, followed by analysis of data it was revealed that hyperlipidemia with increased liver and cardiac marker enzymes, are associated with hepatocellular injury and cardiac damage. The data also supported increased proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). As oxidative stress parameter increased in both liver and heart, there is also an increased in TNF-α due to an increased expression of inducible nitric oxide (NO) synthase, which led to a high production of NO. Moreover, HLD treatment explicitly weakens reasonability of hepatocytes and cardiomyocytes conceivably through G0/G1 or S stage capture or perhaps by means of enlistment of sub-G0/G1 DNA fragmentation and a sign of apoptosis. Conclusions Based on the outcomes, it tends to be inferred that consequences of the present examination uncovered HLD in combination of 2:3 applies most encouraging systemic damage by reactive oxygen species generation and hyperlipidemia and necroapoptosis of the liver and heart. Hence, outcome of this study may help to formulate health care strategy and warns about the food habit in universal population regarding the use of hydrogenated and saturated fats (vanaspati ghee) in diet.

Evaluation of Antimicrobial Efficacy of various Intracanal Medicaments in Primary Teeth: An in vivo Study.

INTRODUCTION: Bacteria and their products play a primary etiological role in the initiation and perpetuation of pulpoperiapical pathosis. Intracanal medication is important for endodontic success as it eliminates microorganisms that persist after chemomechanical preparation. AIM: To compare antimicrobial efficacy of calcium hydroxide powder, triple antibiotic paste, calcium hydroxide with 2% chlorhexidine solution, and triple antibiotic paste with 2% chlorhexidine solution. MATERIALS AND METHODS: A total of 48 nonvital primary teeth were included in this study. After access opening first microbiological sample (s1) was collected by using absorbent paper point introducing into canal. Second microbilogical sample (s2) was taken following chemomechanical preparation and the teeth were divided into four groups: Group I: calcium hydroxide (CH) powder with distilled water; group II: CH with 2% chlorhexidine solution; group III: triple antibiotic powder with distilled water; group IV: triple antibiotic paste with 2% chlorhexidine solution. Then the canals were filled with any one group of the medicament and cavity was temporarily sealed with zinc oxide eugenol. After 1 week, a postmedication sample (s3) was collected. Then the canal was filled with Metapex, restored with glass ionomer cement. CONCLUSION: From the experiments carried out in this study, with the limitations, an inference can be drawn that a combination of antimicrobial agent used as intracanal medicament is definitely better than single agent like Ca(OH)2. HOW TO CITE THIS ARTICLE: Dutta B, Dhull KS, Das D, Samir PV, Verma RK, Singh N. Evaluation of Antimicrobial Efficacy of various Intracanal Medicaments in Primary Teeth: An in vivo Study. Int J Clin Pediatr Dent 2017;10(3):267-271.

Telavancin: a novel semisynthetic lipoglycopeptide agent to counter the challenge of resistant Gram-positive pathogens.

Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA (S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis). Telavancin has two proposed mechanisms of action. In vitro, telavancin has a rapid, concentration-dependent bactericidal effect, due to disruption of cell membrane integrity. Telavancin has demonstrable in vitro activity against aerobic and anaerobic Gram-positive bacteria. Telavancin and vancomycin have similar spectra of activity. Gram-negative bacteria are usually non-susceptible to telavancin. Telavancin has been successfully tested in various animal models of bacteremia, endocarditis, meningitis, and pneumonia. Phase II Telavancin versus Standard Therapy for Treatment of Complicated Skin and Soft-Tissue Infections due to Gram-Positive Bacteria (FAST 1 and FAST 2) and phase III [Assessment of Telavancin in Complicated Skin and Skin Structure Infections 1 (ATLAS 1 and ATLAS 2)] clinical trials have been conducted for evaluating telavancin's efficacy and safety in cSSSIs. Phase III clinical trials have been carried out for evaluating telavancin's safety and efficacy in nosocomial pneumonia [Assessment of Telavancin for Treatment of Hospital acquired Pneumonia 1 and 2 (ATTAIN 1 and ATTAIN 2)]. A phase II randomized, double-blind, clinical trial has been carried out for evaluating telavancin's safety and efficacy in uncomplicated S. aureus bacteremia [Telavancin for Treatment of Uncomplicated S. aureus Bacteremia (ASSURE)]. Pacemaker lead-related infective endocarditis due to a vancomycin intermediate S. aureus (VISA) strain (non-daptomycin susceptible) was successfully treated with parenteral telavancin for 8 weeks. Telavancin extensively binds to serum albumin (~93%) and has a relatively small volume of distribution. Telavancin is not biotransformed by any cytochrome P450 microsomal enzymes and excreted mainly in the urine. Though well-tolerated, worrisome adverse effects, including renal dysfunction and QTc prolongation are of potential concern. Given its extensive binding to plasma proteins, long half-life, and a long post-antibiotic effect, it represents a promising addition to the therapeutic armamentarium in combating infections caused by resistant Gram-positive pathogens, namely, MRSA.

Possible involvement of iNOS and TNF-α in nutritional intervention against nicotine-induced pancreatic islet cell damage.

Nicotine is the more abundant and most significant components of cigarette smoke. Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic injury. Although effects of smoking on endocrine pancreas are still controversial Here, we examined the impact and underlying mechanisms of action of folic acid and vitamin B12 on nicotine induced damage in pancreatic islets of rats. Male Wistar rats were treated with nicotine (3mg/kg body weight/day, intraperitonealy) with or without folic acid (36µg/kg body weight/day, orally) and vitamin B12 (0.63µg/kg body weight/day, orally) for 21days. Supplementation with folic acid and vitamin B12 suppressed the nicotine induced changes in HbA1c, insulin, TNF-α, IL-6, generation of reactive oxygen species, and attenuated the changes in markers of oxidative stress. Moreover, folic acid and vitamin B12 also counteracted the increased expression of protein and mRNA contents of TNF-α and iNOS produced by nicotine. Further, folic acid and vitamin B12 in combination limits the nicotine induced changes in cell cycle and excessive apoptosis of the pancreatic ß-cells and also successfully blunted the nicotine induced alteration in loss of mitochondrial membrane potential. In conclusion, data demonstrate that folic acid and vitamin B12 may be possible nutritional intervention against cellular oxidative stress, which is a critical step in nicotine-mediated islet injury, and improves islet cell functional status by scavenging free radicals and by inhibiting the generation of pro-inflammatory mediators.