Baseline findings of a multicentric ambispective cohort study (2021-2022) among hospitalised mucormycosis patients in India.

In India, the incidence of mucormycosis reached high levels during 2021-2022, coinciding with the COVID-19 pandemic. In response to this, we established a multicentric ambispective cohort of patients hospitalised with mucormycosis across India. In this paper, we report their baseline profile, clinical characteristics and outcomes at discharge. Patients hospitalized for mucormycosis during March-July 2021 were included. Mucormycosis was diagnosed based on mycological confirmation on direct microscopy (KOH/Calcofluor white stain), culture, histopathology, or supportive evidence from endoscopy or imaging. After consent, trained data collectors used medical records and telephonic interviews to capture data in a pre-tested structured questionnaire. At baseline, we recruited 686 patients from 26 study hospitals, of whom 72.3% were males, 78% had a prior history of diabetes, 53.2% had a history of corticosteroid treatment, and 80% were associated with COVID-19. Pain, numbness or swelling of the face were the commonest symptoms (73.3%). Liposomal Amphotericin B was the commonest drug formulation used (67.1%), and endoscopic sinus surgery was the most common surgical procedure (73.6%). At discharge, the disease was stable in 43.3%, in regression for 29.9% but 9.6% died during hospitalization. Among survivors, commonly reported disabilities included facial disfigurement (18.4%) and difficulties in chewing/swallowing (17.8%). Though the risk of mortality was only 1 in 10, the disability due to the disease was very high. This cohort study could enhance our understanding of the disease's clinical progression and help frame standard treatment guidelines.

Aneurysms of Aortic Sinus of Valsalva Dissecting Through the Interventricular Septum With Rupture into the Left Ventricle: Case Series and Literature Review.

Aneurysm of Aortic sinus of Valsalva (ASOV) dissecting into the interventricular septum (IVS) and rupturing into the left ventricle (LV) is a rare clinical diagnosis. Systemic inflammatory diseases like tuberculosis can aggravate this condition. We describe three cases of ASOV dissecting into the IVS and rupturing into the LV. All three patients underwent surgical intervention; two had a successful outcome. A literature review was conducted and19 previously reported cases were studied. The extent and direction of septal dissection determined the associated cardiac valvular and rhythm problems. Patch closure of the mouth of the aneurysm is the surgical method of choice. In the presence of multiple sinus tracts or if there is recurrence after surgical closure, aortic sinus or root replacement techniques have better outcomes.

Nanosensor based approaches for quantitative detection of heparin.

Heparin, being a widely employed anticoagulant in numerus clinical complications, requires strict quantification and qualitative screening to ensure the safety of patients from potential threat of thrombocytopenia. However, the intricacy of heparin's chemical structures and low abundance hinders the precise monitoring of its level and quality in clinical settings. Conventional laboratory assays have limitations in sensitivity and specificity, necessitating the development of innovative approaches. In this context, nanosensors emerged as a promising solution due to enhanced sensitivity, selectivity, and ability to detect heparin even at low concentrations. This review delves into a range of sensing approaches including colorimetric, fluorometric, surface-enhanced Raman spectroscopy, and electrochemical techniques using different types of nanomaterials, thus providing insights of its principles, capabilities, and limitations. Moreover, integration of smart-phone with nanosensors for point of care diagnostics has also been explored. Additionally, recent advances in nanopore technologies, artificial intelligence (AI) and machine learning (ML) have been discussed offering specificity against contaminants present in heparin to ensure its quality. By consolidating current knowledge and highlighting the potential of nanosensors, this review aims to contribute to the advancement of efficient, reliable, and economical heparin detection methods providing improved patient care.

Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities.

SCLC is refractory to conventional therapies; targeted therapies and immunological checkpoint inhibitor (ICI) molecules have prolonged survival only marginally. In addition, ICIs help only a subgroup of SCLC patients. Different types of kinases play pivotal roles in therapeutics-driven cellular functions. Therefore, there is a significant need to understand the roles of kinases in regulating therapeutic responses, acknowledge the existing knowledge gaps, and discuss future directions for improved therapeutics for recalcitrant SCLC. Here, we extensively review the effect of dysregulated kinases in SCLC. We further discuss the pharmacological inhibitors of kinases used in targeted therapies for recalcitrant SCLC. We also describe the role of kinases in the ICI-mediated activation of antitumor immune responses. Finally, we summarize the clinical trials evaluating the potential of kinase inhibitors and ICIs. This review overviews dysregulated kinases in SCLC and summarizes their potential as targeted therapeutic agents. We also discuss their clinical efficacy in enhancing anticancer responses mediated by ICIs.

Growth, ultrastructural and physiological characteristics of Abelmoschus cytotypes under elevated ozone stress: a study on ploidy-specific responses.

Tropospheric ozone (O3 ) is a significant abiotic stressor whose rising concentration negatively influences plant growth. Studies related to the differential response of Abelmoschus cytotypes to elevated O3 treatment are scarce and need further exploration to recognise the role of polyploidisation in stress tolerance. In this study, we analysed the changes in growth pattern, ultrastructure, physiology and foliar protein profile occurring under O3 stress in Abelmoschus moschatus (monoploid), Abelmoschus esculentus (diploid) and Abelmoschus caillei (triploid). Our findings showed that higher stomatal conductance in A. moschatus triggered higher O3 intake, causing damage to stomatal cells and photosynthetic pigments. Additionally, it caused a reduction in photosynthetic rates, leading to reduced plant growth, total biomass and economic yield. This O3 -induced toxicity was less in diploid and triploid cytotypes of Abelmoschus . Protein profiling by sodium dodecyl sulpate-polyacrylamide gel electrophoresis showed a significant decrease in the commonly found RuBisCO larger and smaller subunits. The decrease was more prominent in monoploid compared to diploid and triploid. This study provides crucial data for research that aim to enhance plant ability to withstand O3 induced oxidative stress. Our findings may help in developing a tolerant variety through plant breeding techniques, which will be economically more advantageous in reaching the objective of sustainable production at the high O3 levels projected under a climate change scenario.

4-(Benzyloxy)phenol-induced p53 exhibits antimycobacterial response triggering phagosome-lysosome fusion through ROS-dependent intracellular Ca2+ pathway in THP-1 cells.

Drug-resistant tuberculosis (TB) outbreak has emerged as a global public health crisis. Therefore, new and innovative therapeutic options like host-directed therapies (HDTs) through novel modulators are urgently required to overcome the challenges associated with TB. In the present study, we have investigated the anti-mycobacterial effect of 4-(Benzyloxy)phenol. Cell-viability assay asserted that 50 µM of 4-(Benzyloxy)phenol was not cytotoxic to phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 (dTHP-1) cells. It was observed that 4-(Benzyloxy)phenol activates p53 expression by hindering its association with KDM1A. Increased ROS, intracellular Ca2+ and phagosome-lysosome fusion, were also observed upon 4-(Benzyloxy)phenol treatment. 4-(Benzyloxy)phenol mediated killing of intracellular mycobacteria was abrogated in the presence of specific inhibitors of ROS, Ca2+ and phagosome-lysosome fusion like NAC, BAPTA-AM, and W7, respectively. We further demonstrate that 4-(Benzyloxy)phenol mediated enhanced ROS production is mediated by acetylation of p53. Blocking of p53 acetylation by Pifithrin-α (PFT- α) enhanced intracellular mycobacterial growth by blocking the mycobactericidal effect of 4-(Benzyloxy)phenol. Altogether, the results showed that 4-(Benzyloxy)phenol executed its anti-mycobacterial effect by modulating p53-mediated ROS production to regulate phagosome-lysosome fusion through Ca2+ production.

Use of the subfascial plane in debulking an extensive lower extremity plexiform neurofibroma: A case report.

INTRODUCTION: Plexiform neurofibromas (PNs) are characterized by their diffuse masses with tortuous expansion along nerve branches. While surgery is the primary management for PNs, the optimal surgical approach remains unestablished. CASE PRESENTATION: A 35-year-old lady presented with a large hanging mass covering the medial aspect of the thigh and the leg. It caused discomfort, disfigurement, and occasional pain. The patient was planned for the debulking surgery under spinal anesthesia. Incisions were given on the normal-looking skin adjacent to the mass, through the skin layers, subcutaneous tissue and deep fascia until the muscles were seen. The mass was then approached and elevated in the subfascial plane (relatively avascular). Large, dilated, dense tortuous vessels could be seen in the suprafascial and subcutaneous planes. Maximum area that could be removed was marked and excised. The normal contour of the left lower extremity was restored close to achieving a thigh and a leg lift. DISCUSSION: PNs pose surgical challenges due to their vascularity and difficult locations. The subfascial debulking approach presented in the case aims to reduce intraoperative hemorrhage by avoiding highly vascular areas and preventing entry into blood sinuses within the neurofibromatous tissue. This technique also minimizes the risk of inadvertent injury to nearby neurovascular structures. CONCLUSION: The proposed subfascial approach, significantly reduces intraoperative hemorrhage during the debulking of a PN.

Targeting chemokine-receptor mediated molecular signaling by ethnopharmacological approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Infection and inflammation are critical to global human health status and the goal of current pharmacological interventions intends formulating medications/preventives as a measure to deal with this situation. Chemokines and their cognate receptors are major regulatory molecules in many of these ailments. Natural products have been a keen source to the drug development industry, every year contributing significantly to the growing list of FDA approved drugs. A multiverse of natural resource is employed as a part of curative regimen in folk/traditional/ethnomedicine which can be employed to discover, repurpose, and design potent medications for the diseases of clinical concern. AIM OF THE STUDY: This review aims to systematically document the ethnopharmacologically active agents targeting the infectious-inflammatory diseases through the chemokine-receptor nexus. MATERIALS AND METHODS: Articles related to chemokine/receptor modulating ethnopharmacological anti-inflammatory, anti-infectious natural sources, bioactive compounds, and formulations have been examined with special emphasis on women related diseases. The available literature has been thoroughly scrutinized for the application of traditional medicines in chemokine associated experimental methods, their regulatory outcomes, and pertinence to women's health wherever applicable. Moreover, the potential traditional regimens under clinical trials have been critically assessed. RESULTS: A systematic and comprehensive review on the chemokine-receptor targeting ethnopharmaceutics from the available literature has been provided. The article discusses the implication of traditional medicine in the chemokine system dynamics in diverse infectious-inflammatory disorders such as cardiovascular diseases, allergic diseases, inflammatory diseases, neuroinflammation, and cancer. On this note, critical evaluation of the available data surfaced multiple diseases prevalent in women such as osteoporosis, rheumatoid arthritis, breast cancer, cervical cancer and urinary tract infection. Currently there is no available literature highlighting chemokine-receptor targeting using traditional medicinal approach from women's health perspective. Moreover, despite being potent in vitro and in vivo setups there remains a gap in clinical translation of these formulations, which needs to be strategically and scientifically addressed to pave the way for their successful industrial translation. CONCLUSIONS: The review provides an optimistic global perspective towards the applicability of ethnopharmacology in chemokine-receptor regulated infectious and inflammatory diseases with special emphasis on ailments prevalent in women, consecutively addressing their current status of clinical translation and future directions.

Awakening the sleeping giant: Epstein-Barr virus reactivation by biological agents.

Epstein-Barr virus (EBV) may cause harm in immunocompromised conditions or on stress stimuli. Various chemical agents have been utilized to induce the lytic cycle in EBV-infected cells. However, apart from chemical agents and external stress stimuli, certain infectious agents may reactivate the EBV. In addition, the acute infection of other pathogens may provide suitable conditions for EBV to thrive more and planting the roots for EBV-associated pathologies. Various bacteria such as periodontal pathogens like Aggregatibacter, Helicobacter pylori, etc. have shown to induce EBV reactivation either by triggering host cells directly or indirectly. Viruses such as Human simplex virus-1 (HSV) induce EBV reactivation by HSV US3 kinase while other viruses such as HIV, hepatitis virus, and even novel SARS-CoV-2 have also been reported to cause EBV reactivation. The eukaryotic pathogens such as Plasmodium falciparum and Aspergillus flavus can also reactivate EBV either by surface protein interaction or as an impact of aflatoxin, respectively. To highlight the underexplored niche of EBV reactivation by biological agents, we have comprehensively presented the related information in this review. This may help to shedding the light on the research gaps as well as to unveil yet unexplored mechanisms of EBV reactivation.

A review on multifaceted biomedical applications of heparin nanocomposites: Progress and prospects.

Advances in polymer-based nanocomposites have revolutionized biomedical applications over the last two decades. Heparin (HP), being a highly bioactive polymer of biological origin, provides strong biotic competence to the nanocomposites, broadening the horizon of their applicability. The efficiency, biocompatibility, and biodegradability properties of nanomaterials significantly improve upon the incorporation of heparin. Further, inclusion of structural/chemical derivatives, fractionates, and mimetics of heparin enable fabrication of versatile nanocomposites. Modern nanotechnological interventions have exploited the inherent biofunctionalities of heparin by formulating various nanomaterials, including inorganic/polymeric nanoparticles, nanofibers, quantum dots, micelles, liposomes, and nanogels ensuing novel functionalities targeting diverse clinical applications involving drug delivery, wound healing, tissue engineering, biocompatible coatings, nanosensors and so on. On this note, the present review explicitly summarises the recent HP-oriented nanotechnological developments, with a special emphasis on the reported successful engagement of HP and its derivatives/mimetics in nanocomposites for extensive applications in the laboratory and health-care facility. Further, the advantages and limitations/challenges specifically associated with HP in nanocomposites, undertaken in this current review are quintessential for future innovations/discoveries pertaining to HP-based nanocomposites.

Aortic Origin of a Branch Pulmonary Artery: Early and Mid-Term Single Center Outcomes.

BACKGROUND: Anomalous origin of pulmonary artery (AOPA) is a rare congenital cardiac anomaly. It requires early surgical intervention (<6 months) to prevent irreversible pulmonary vaso-occlusive disease. This study was conducted to determine the surgical outcomes of this rare and intriguing anomaly. METHODS: From January 2015 to 2022, we have studied, 20 patients who underwent surgical correction for this anomaly with a mean age of 6.25 ± 3.7 months. There were 12 patients of <6 months of age. Their preoperative, intraoperative, and postoperative data were collected. They were followed up at every three months for the first year, every six months for two years, and then annually. RESULTS: Among three early mortalities, two were operated before six months of age and one was older than six months (ten months). Those patients presented after six months had longer ventilation time (P = .001). There was no difference in their pulmonary artery pressure (P = .06), right ventricle systolic pressure (RVSP) (P = .85), postoperative saturation (P = .51), inotropic score (P = .06), hospital and intensive care unit stay (P > .05), or mortality (P = .79). There was no late mortality at mean follow-up of 51.31 ± 20.27 months with Kaplan-Meier survival of 85% at 1, 5, and ten years. All patients were asymptomatic, with normal biventricular function and RVSP. One patient required balloon dilatation of the anastomotic site, with Kaplan-Meier event-free survival of 100% at one year, 92% at five and ten years. CONCLUSION: Surgical correction of AOPA in patients beyond six months is still feasible with a higher early morbidity and comparable mortality with good clinical and echocardiographical outcomes at mid-term follow-up.

Early onset of aridity in the past millennium: Insights from vegetation dynamics and climate change in the alpine, cold-desert region of Trans Himalaya, India.

Palynological analysis of surface soil and sub-surface sediments from the outwash plain of Hamtah Glacier, Lahaul-Spiti, India, has brought out the vegetation and climatic changes in the area during the last 1580 years. The arboreal and non-arboreal pollen ratio (AP/NAP) has been used to demarcate the different vegetation and climatic zones, complemented by the frequencies of the broad-leaved taxa. Lower values of thermophilous, broad-leaved arboreal taxa, indicate that the region experienced cold-arid conditions between 1580 and 1330 yr BP (AD 370-620); which can be related to the Dark Ages Cold Period (DACP). Thereafter, between 1330 and 950 yr BP (AD 620-1000), a rejuvenation of the broad-leaved elements reflects the initiation of a comparatively warm and moist phase, marking the Medieval Climatic Anomaly (MCA) in the region. The warm-moist phase was, however, short-lived, and from 950 yr BP to the Present (AD 1000 onwards), the region saw a return to cold-arid conditions, as evidenced by a sharp fall in the AP/NAP ratio. This cold-arid phase was, nevertheless, punctuated by a warm-moist period during 790 to 680 yr BP (AD 1160-1270), which marks the terminal phase of the MCA. After the termination of the MCA, the Little Ice Age (LIA) is well-marked in the area. The culmination of the long cold-arid regime is characterized by warmer conditions over the last 160 years, which is the manifestation of the Current Warm Period (CWP). Magnetic susceptibility (χlf) and sediment geochemistry (Weathering Index of Parker) were also attempted to have a multi-proxy approach, and show a general compatibility with the palynological data. The palaeoclimatic evidences suggest shorter warm periods and extended colder phases during the last 1580 years; in this high-altitude, cold-desert, Trans Himalayan region.

Clinical Features, Laboratory Characteristics and Outcome from Oral Contraceptives-induced Liver Injury in 43 Consecutive Patients and a Brief Review of Published Reports.

Background: Hormonal oral contraceptive (OC) agents such as estrogen or progesterone, either as single agents or in combination, and a non-hormonal drug like ormeloxifene are used for various conditions. However, estrogen and progesterone-containing OC as well as ormeloxifene are seldom associated with hepatotoxicity. We prospectively studied the clinical, demographic, liver injury pattern, complications, and outcome of the hepatotoxicity from OC and ormeloxifene. Methods: We analyzed and compared the aforementioned characteristics among consecutive patients with OC and ormeloxifene-induced drug-induced liver injury (DILI) from two university hospitals in India. Cases fulfilling established DILI criteria and the Roussel Uclaf causality assessment method were identified and followed up until recovery/death. Results: We identified 43 (3.5%) amongst 1226 patients with DILI; 19 (44%) from estrogen and progesterone combination, 21 (49%) from progesterone monotherapy, and 3 (7%) due to ormeloxifene. Seven cases were identified from 1998 to 2014 and 36 cases from 2015 to 2023. All were due to oral tablets. The mean age was 36 years (range 21-75). Nineteen patients (44%) developed jaundice and 5 (11.6%) developed itching. The liver injury pattern was hepatocellular in 19 (44%), mixed in 13 (30%), and cholestatic in 11 (26%). Four patients (9%) died, three from acute liver failure and one due to acute on chronic liver failure. Liver biochemical tests normalized after a mean of 66 days after stopping the implicated agents. Contrastingly, literature search yielded 24 cases of progesterone DILI reported between 1962 and 2019 with no mortality. Conclusion: In contrast to published literature on oral contraceptives, a majority of oral contraceptive-induced DILI in our series were from progesterone monotherapy and a smaller number with ormeloxifene, that often resulted in clinically significant jaundice or liver test abnormalities and rarely in fatality.

Pseudoxanthoma elasticum and retinitis pigmentosa in a patient with a novel mutation in the ABCC6 gene.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition caused by mutations in the ABCC6 gene. Ocular features include angioid streaks, peau d'orange fundus, and drusen. We report a novel ABCC6 mutation causing PXE in a patient with a mixed phenotype of PXE and retinitis pigmentosa (RP). CASE: A 37-year-old female presented with decreased peripheral vision and nyctalopia. Ocular imaging revealed angioid streaks emanating from the optic nerve as well as peripheral pigmentary changes and bone spicules. Genetic testing revealed two mutations in ABCC6 in trans. No other mutation was identified. CONCLUSION: We present a rare case with ocular findings of PXE and RP in a patient with a novel ABCC6 mutation. The patient presented both with peripheral pigmentary changes and angioid streaks. Further investigation into this novel mutation would be beneficial to determine if the mutation is involved in the RP phenotype.

Early and mid-term outcomes of double-chambered right ventricle repair: An 8-year experience.

BACKGROUND/AIM: Double-chambered right ventricle is a rare and progressive condition that is characterised by obstruction of the right ventricular tract. Double-chambered right ventricle is usually associated with ventricular septal defect. Early surgical intervention is recommended in patients with these defects. Based on this background, the present study aimed to review early and midterm outcomes of primary repair after double-chambered right ventricle. METHODS: Between January 2014 and June 2021, 64 patients with a mean age of 13.42 ± 12.31 years underwent surgical repair for double-chambered right ventricle. The clinical outcomes of these patients were reviewed and assessed retrospectively. RESULTS: An associated ventricular septal defect was present in all the recruited patients; 48 (75%) patients of sub-arterial type, 15 (23.4%) of perimembranous, and 1 (1.6%) patient of muscular type. The patients were followed up for a mean period of 46.73 ± 27.37 months. During their follow-up, a significant decrease in the mean pressure gradient from 62.33 ± 5.52 mmHg preoperatively to 15.73 ± 2.94 mmHg postoperatively was observed (p < 0.001). Notably, there were no hospital deaths. CONCLUSIONS: The development of double-chambered right ventricle in association with ventricular septal defect results in an increased pressure gradient within the right ventricle. The defect needs correction in a timely manner. In our experience, the surgical correction of double-chambered right ventricle is safe and shows excellent early and mid-term results.

Lanosterol elevates cytoprotective response through induced-proteasomal degradation of aberrant proteins.

Efficient protein synthesis is a basic requirement of our cells to replace the old or defective proteins from the intrinsic crowded biomolecular environment. The interconnection among synthesis, folding, and degradation of proteins represents central paradigm to proteostasis. Failure of protein quality control (PQC) mechanisms results in the disturbance and inadequate functions of proteome. The consequent misfolded protein accumulation can form the basis of neurodegeneration onset and largely represents imperfect aging. Understanding how cells improve the function of deregulated PQC mechanisms to establish and maintain proteostasis against the unwanted sequestration of normal proteins with misfolded proteinaceous inclusions is a major challenge. Here we show that treatment of Lanosterol, a cholesterol synthesis pathway intermediate, induces Proteasome proteolytic activities and, therefore, supports the PQC mechanism for the elimination of intracellular aberrant proteins. The exposure of Lanosterol not only promotes Proteasome catalytic functions but also elevates the removal of both bona fide and neurodegenerative diseases associated toxic proteins. Our current study suggests that increasing Proteasome functions with the help of small molecules such as Lanosterol could serve as a cytoprotective therapeutic approach against abnormal protein accumulation. Cumulatively, based on findings in this study, we can understand the critical importance of small molecules and their potential therapeutic influence in re-establishing disturbed proteostasis linked with neurodegeneration.

Comparison of Endophthalmitis Rates after Alcohol-Based Chlorhexidine and Povidone-Iodine Antisepsis for Intravitreal Injections.

OBJECTIVE: Intravitreal injections (IVIs) are the most frequently performed intraocular procedure in Canada. Povidone-iodine (PI) is the current gold standard for antisepsis for IVI and is widely used; chlorhexidine (CH) is a possible alternative antiseptic agent. This study aims to compare rates of endophthalmitis after IVI with 0.05% chlorhexidine with a 4% alcohol base antisepsis to rates of endophthalmitis after IVI with 10% PI antisepsis. DESIGN: Retrospective cohort study. SUBJECTS: Eyes that received IVI between May 2019 and October 2022 at a group retina practice in Edmonton, Canada. METHODS: Eyes at a single center received focal conjunctival application of either 10% PI antisepsis or 0.05% CH in 4% alcohol antisepsis for 30 seconds before each IVI. MAIN OUTCOME MEASURE: Rates of endophthalmitis between the PI and CH groups. RESULTS: A total of 170 952 IVIs were performed during the study period. A total of 31 135 were performed using CH prophylaxis compared with 139 817 with PI prophylaxis. Among all IVIs there were 49 total cases of endophthalmitis, 29 in the PI group (0.021%) and 20 in the CH group (0.064%). There was a statistically significant difference in the rates of endophthalmitis between the 2 groups (P < 0.001). The odds ratio for developing endophthalmitis with CH antisepsis was 3.1 (95% confidence interval, 1.9-5.2) compared with PI antisepsis. There were increased odds of developing endophthalmitis with aflibercept injection compared with bevacizumab (odds ratio, 3.48; 95% confidence interval, 2.09-7.24). CONCLUSIONS: There is a statistically significant difference in rates of endophthalmitis between alcohol-based CH and PI antisepsis for IVI in our patient population utilizing the methods discussed. In our center, alcohol-based CH is now considered a second-line antiseptic agent. Further studies are warranted to further assess the endophthalmitis rate utilizing these 2 antiseptic agents. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Helicobacter pylori and Epstein-Barr virus infection in cell polarity alterations.

The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-ß/SMAD, and ß-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells.

The Emerging Role of Toll-Like Receptor-Mediated Neuroinflammatory Signals in Psychiatric Disorders and Acquired Epilepsy.

The new and evolving paradigms of psychiatric disorders pathogenesis are deeply inclined toward chronic inflammation that leads to disturbances in the neuronal networks of patients. A strong association has been established between the inflammation and neurobiology of depression which is mediated by different toll-like receptors (TLRs). TLRs and associated signalling pathways are identified as key immune regulators to stress and infections in neurobiology. They are a special class of transmembrane proteins, which are one of the broadly studied members of the Pattern Recognition Patterns family. This review focuses on summarizing the important findings on the role of TLRs associated with psychotic disorders and acquired epilepsy. This review also shows the promising potential of TLRs in immune response mediated through antidepressant therapies and TLRs polymorphism associated with various psychotic disorders. Moreover, this also sheds light on future directions to further target TLRs as a therapeutic approach for psychiatric disorders.