Complex dichotomous links of nonalcoholic fatty liver disease and inflammatory bowel disease: exploring risks, mechanisms, and management modalities.

Nonalcoholic fatty liver disease (NAFLD) has been shown to be linked to inflammatory bowel disease (IBD) due to established risk factors such as obesity, age, and type 2 diabetes in numerous studies. However, alternative research suggests that factors related to IBD, such as disease activity, duration, and drug-induced toxicity, can contribute to NAFLD. Recent research findings suggest IBD relapses are correlated with dysbiosis, mucosal damage, and an increase in cytokines. In contrast, remission periods are characterized by reduced metabolic risk factors. There is a dichotomy evident in the associations between NAFLD and IBD during relapses and remissions. This warrants a nuanced understanding of the diverse influences on disease manifestation and progression. It is possible to provide a holistic approach to care for patients with IBD by emphasizing the interdependence between metabolic and inflammatory disorders.

Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis.

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices-such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass-require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.

In Vitro Characterisation Revealed Himalayan Dairy Kluyveromyces marxianus PCH397 as Potential Probiotic with Therapeutic Properties.

Recently, probiotics have gained much attention for their roles against various clinical conditions. Obesity is a worldwide health problem that triggers various other major complications like type 2 diabetes (T2D) and cancers, including colorectal cancer (CRC). Earlier, Kluyveromyces marxianus PCH397 isolated from yak (Bos grunniens) milk has been characterised by us for its efficient ß-galactosidase-producing ability, an important probiotic property. In the present study, yeast PCH397 has been evaluated for various parameters for its probiotic use. PCH397 exhibited tolerance to GI tract conditions (low pH, pancreatin, pepsin, and bile salts) with 78 to 99% survivability, possessed around 81% cell surface hydrophobicity, and 96% autoaggregation ability. The cell-free extract (CFE) and cell-free supernatant (CFS) from PCH397 improved insulin sensitisation by enhancing 2-NBDG (a glucose analogue) uptake in 3T3-L1 adipocytes, an approach useful in T2D treatment. They also exhibited lower intracellular lipid accumulation, triglyceride storage, and reactive oxygen species in differentiated adipocytes, indicating their anti-adipogenic ability. Also, CFE and intact cells (ICs) exhibited 73.33 ± 1.11% and 34.88 ± 2.80% DPPH radical scavenging activity, respectively. Furthermore, CFS showed a cytotoxic effect on SW-480 colorectal cancer (CRC) cells and induced the cell cycle phase arrest after 24 h of treatment. In conclusion, these results demonstrate that K. marxianus PCH397 could be used as a potential probiotic yeast and presents a therapeutic potential against obesity, T2D, and colon cancer.

Phloretin mitigates oxidative injury, inflammation, and fibrogenic responses via restoration of autophagic flux in in vitro and preclinical models of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) with growing incidences is a major health concern worldwide. Alteration in cellular redox homeostasis and autophagy plays a critical role in the progression of NAFLD to more severe outcomes. The lack of safe and effective therapy for the disease necessitates the exploration of new therapeutic compounds. Therefore, in the present study, we investigated the potential of phloretin to maintain redox equilibrium and prevent disease progression via modulation of autophagy in NAFLD. Free fatty acid exposed Huh7 cells were used to evaluate the efficacy of phloretin in vitro. Further, phloretin was administered orally to western diet induced NAFLD in C57BL/6J mice at different doses. The chronic exposure to fatty acids and the western diet triggered lipid accumulation in the Huh7 cells and western diet-fed mice liver, respectively. In addition, mitochondrial dysfunction, oxidative stress, inflammation and decreased hepatic autophagy were observed in disease condition. Phloretin encouraged autophagy mediated hepatic lipid clearance and restored mitochondrial membrane potential and redox homeostasis. It also reduced histological injury by reducing hepatic lipogenesis and facilitating fatty acid oxidation. Moreover, findings of the study also revealed the mitigatory effect of phloretin on inflammatory and fibrogenic markers. Altogether, the study suggested that phloretin effectively attenuates NAFLD progression via upregulating autophagy-mediated lipid breakdown and inhibits oxidative damage, hepatic inflammation and fibrosis.

Long-term consumption of green tea EGCG enhances murine health span by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis, and immunosenescence.

Cellular senescence is emerging as a major hallmark of aging, and its modulation presents an effective anti-aging strategy. This study attempted to understand the progression of cellular senescence in vivo, and whether it can be mitigated by chronic consumption of green tea catechin epigallocatechin gallate (EGCG). We profiled cellular senescence in various organs of mice at four different time-points of lifespan, and then explored the influence of EGCG consumption in impacting markers of cellular senescence, inflamm-aging, immunosenescence, and gut dysbiosis. We report that visceral adipose and intestinal tissues are highly vulnerable to cellular senescence due to an increase in DNA damage response, activation of cell cycle inhibitors, and senescence-associated secretory phenotype regulators. With advancing age, dysregulation in nutrient signaling mediators (AMPK/AKT/SIRT3/5), and a decrease in autophagy was also observed. Inflamm-aging markers (TNF-α/IL-1ß) and splenic CD4/CD8 T cell ratio increased with age, while NK cell population decreased. Metagenomic analyses revealed an age-related decrease in the diversity of microbial species and an increase in the abundance of various pathogenic bacterial species. On the other hand, long-term EGCG consumption significantly attenuated markers of DNA damage, cell cycle inhibitors, senescence-associated secretory phenotype regulators, AMPK/AKT signaling, and enhanced SIRT3/5 expression and autophagy. Systemic inflamm-aging indicators decreased, while early T cell activation increased in EGCG fed animals. EGCG also suppressed the abundance of pathogenic bacteria and preserved microbial diversity. Our results suggest that adipose and intestine tissues are prone to cellular senescence and that chronic consumption of EGCG can attenuate several deleterious aspects of aging which could be implicated in developing anti-aging strategies.

Assessing the risk of thromboembolism in cancer patients receiving immunotherapy.

Malignancy has long been implicated with hypercoagulability, leading to an increased rate of both venous and arterial thromboembolic events (VTE and ATE). Immunotherapy has established itself as a cornerstone of modern cancer therapy by promoting antitumor immune responses, though there have been some suggestions that immune-related adverse events could include increased rates of VTE and ATE. In this review, we examine the available evidence regarding the use of immune checkpoint inhibitors (ICIs) and thrombosis. First, we describe the potential mechanisms by which ICIs might lead to thrombophilia given the overlap between the immune system, coagulation cascade, and platelet adhesion and activation. In addition, while there are some preclinical data evaluating immunotherapy-associated ATEs in animal models, there is a paucity of evidence exploring potential mechanism of VTEs in ICIs. Second, we review the incidence of ATE and VTE in patients receiving ICIs in the published literature. Finally, we discuss current limitations in understanding, areas of conflicting evidence, and approaches to further investigation.

Experimental performance evaluation of an impinging jet with fins type solar air heater.

The current experimental investigation aimed to evaluate performance of a non-cross flow type solar air heater (SAH). The design comprises of an array of continuous longitudinal fins which extends the bottom of absorber surface and alongside to it a jet plate with inline holes has also been encapsulated. The experiments were performed in natural outdoor conditions for a specified range of flow and geometrical parameters, namely, {[Formula: see text], 5700≤ Re ≤ 11700, 0.046 ≤ Dj/Dh ≤ 0.076, and X/Dh, w/Dh = 0.23, 0.46}, respectively. The key indices such as temperature rise parameter (TRP) and collector thermal efficiency are chosen to analyze the performance characteristics of collector. The influence of the above listed parameters on these constraints has been investigated in details. As a function of the entire range of geometrical parameters, an increase in the air flow rate degrades the value of TRP. At the same situation, collector thermal efficiency was found to increase. The peak values of TRP were obtained between 12:00 and 01:00 pm. The rise in air temperature corresponding to hourly deviation of solar intensity has been interpreted at different fin spacing ratios. Furthermore, a parametric optimization approach is employed to identify the optimum values of fin and jet plate parameters yielding maximum collector thermal efficiency. The obtained data have been worked out to plot the design curves for fin and jet parameters. The experimental results were validated with similar literature. The comparative analysis reports a maximum enhancement in TRP of 20.5 % at Dj/Dh = 0.076. The percentage improvement in collector thermal efficiency of 16.4% at w/Dh = 0.23 and 9.8% at Dj/Dh = 0.076 has also been noted with reference to compared works.

Orthokeratology in Moderate Myopia: A Study of Predictability and Safety.

PURPOSE: Literature is relatively silent on safety profile and predictability of orthokeratology lenses in terms of myopia correction and prevention of further progression, especially in semi-tropical countries; this study was designed to fill this gap. METHODS: This prospective, intervention case series enrolled 30 eyes of 30 patients with myopia up to -5.5 diopters (D). Patients were randomized into two groups of 15 each; the study group was prescribed overnight orthokeratology (OK) lenses, while the control group used daily wear conventional soft contact lenses. Follow-up examinations were performed after 1 h and 6 h, and then at 1, 7, 15, 30 days, and 4 months post lens wear. Uncorrected visual acuity (UCVA), contrast sensitivity, keratometry, central corneal thickness (CCT), and tear film break up time (TBUT) were evaluated at each follow-up examination. RESULTS: All patients attained a visual acuity of 0.00 Logarithm of the Minimum Angle of Resolution (logMAR) after one week of lens use, which was maintained throughout the study period. While patients allotted to the study group had a gain of 8.1 Snellen lines (UCVA), those in the control group gained 8.9 lines (BCVA) at the end of follow-up period. In the OK group, cornea showed a flattening of 0.8 D (mean keratometry) after single overnight usage of OK lens and overall flattening of 1.2 D compared to baseline, at the end of four months. The change in contrast sensitivity, corneal endothelial specular count, axial length and tear film status was not significant in either group. CONCLUSION: Orthokeratology is an effective and safe modality to correct moderate myopia in motivated young adults. No side effects were encountered after a short-term follow-up in participants who resided in semi-tropical environments.

Status of adult immunity to hepatitis A virus in healthcare workers from a tertiary care hospital in north India.

Background & objectives: Humans are considered to be the principal host for hepatitis A virus (HAV) infection. In India, heterogeneous groups of susceptible individuals coexist in different regions. There has been a decline in antibody titres to HAV among young adults which may pose a major public health problem. The objective of this study was to assess the IgG anti-HAV level among healthcare workers (HCWs) in the age group of 20-60 yr and its association with the socio-demographic variables. Methods: Blood sample (2 ml) was collected under aseptic conditions from each participant followed by the preparation of serum and storing at -20°C. ELISA-based kits were used for the determination of IgG antibodies to HAV in the human serum samples. Results: Two hundred and fifty four HCWs were enrolled. IgG anti-HAV antibodies were detected in 97.2 per cent of the samples analyzed. No differences were observed in the levels of IgG anti-HAV antibody and education, income, occupation and socio-economic classes of the HCWs. A seropositivity rate of over 90 per cent was seen amongst all the socio-economic classes. Interpretation & conclusions: High levels of IgG protective antibodies were seen among the studied HCWs, hence HAV vaccination may not be required. It will be advisable to do a cost-benefit analysis of vaccination for HAV.