The Effect of Tuberculosis on the Mortality of Cirrhotic Patients: A Population-Based 3-Year Follow-Up Study

[[abstract]]Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. It is still unknown if TB, like other infectious diseases contributes a poor prognosis in cirrhotic patients. The aim of this study was to investigate the impact of TB on the mortality of cirrhotic patients. National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify 434 cirrhotic patients with new diagnosis of TB between January 1, 2007 and December 31, 2007. The comparison group consisted of 4340 selected cirrhotic patients without TB in the same period by propensity score matching analysis. The 30-day, 90-day, 1-year and 3-year mortalities were 10.1%, 24.2%, 43.1%, and 63% in the TB group, and 7.9%, 15.5%, 31.2%, and 53.4% in the non-TB group. After Cox proportional hazard regression model adjusted by the patients' gender, age, and comorbid disorders, the hazard ratios (HR) in cirrhotic patients with TB for 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortalities were 1.33 [95% confidence interval (CI) 0.97-1.83], 1.91 (95% CI 1.45-2.51), 1.46 (95% CI 1.16-1.84), and 1.10 (95% CI 0.88-1.37), compared to the non-TB group. In conclusion, TB is a risk factor for the mortality of cirrhotic patients. The effect focused on the 30-day to 1-year after diagnosis of TB.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]紙本[[countrycodes]]IN

Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals

<p>Abstract</p> <p>Background</p> <p>The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from <it>S. marianum</it>, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs.</p> <p>Methods</p> <p>Male Wistar albino rats weighing 250–300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin.</p> <p>Results</p> <p>Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs.</p> <p>Conclusion</p> <p>The active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.</p

Trigonelline prevents high cholesterol and high fat diet induced hepatic lipid accumulation and lipo-toxicity in C57BL/6J mice, via restoration of hepatic autophagy.

Non-alcoholic fatty liver disease (NAFLD) is often linked with impaired hepatic autophagy. Here, we studied the alterations in hepatocellular autophagy by high cholesterol and high-fat diet (HC-HF) diet in C57BL/6J mice, and by palmitic acid (PA), in AML-12 and HepG2 cells. Further, we analysed role of Trigonelline (TG), a plant alkaloid, in preventing NAFLD, by modulating autophagy. For this, C57BL/6J mice were fed with Standard Chow (SC) or HC-HF diet, with and without TG for 16 weeks. In-vitro; AML-12 cells and HepG2 cells, were exposed to PA with and without TG, for 24?h. Cellular events related to autophagy, lipogenesis, and lipo-toxicity were studied. The HC-HF diet fed mice showed hepatic autophagy blockade, increased triglycerides and steatosis. PA exposure to AML-12 cells and HepG2 cells induced impaired autophagy, ER stress, resulting in lipotoxicity. TG treatment in HC-HF fed mice, restored hepatic autophagy, and prevented steatosis. TG treated AML-12, and HepG2 cells exposed to PA showed autophagy restoration, and reduced lipotoxicity, however, these effects were diminished in Atg7-/- HepG2 cells, and in the presence of chloroquine. This study shows that HC-HF diet-induced impaired autophagy, and steatosis is prevented by TG, which attributes to its novel mechanism in treating NAFLD

Deciphering the Genome Protection Roles of Autophagy in Primary Human Dermal Fibroblasts (HDFs) against Ultraviolet-(B) –Induced Skin Photodamage

AbstractUltraviolet-B (UV-B) exposure to skin causes photo-damage and acts as the primary etiological agent in photo-carcinogenesis. UV-B exposure induces photodamage in epidermal cells and is the major factor that challenges skin homeostasis. Autophagy allows fundamental adaptation of cells to metabolic needs and stresses. Cellular dysfunction is observed in aged tissues and in toxic insults to cells that undergo through stress. Conversely, promising anti-aging strategies aimed at inhibiting the mTOR pathway has been found to significantly improve the aging related disorders. Recently, autophagy has been found to positively regulate skin homeostasis by enhancing DNA damage recognition. Here we investigated the Geno-protective roles of autophagy in UV-B exposed primary HDFs. We found that improving autophagy levels in HDFs regulates UV-B mediated cellular stress by decreasing the formation of DNA photo adducts, alleviates oxidative and ER stress response and by regulating the expression levels of cell cycle regulatory proteins P21 and P27. Autophagy also prevents HDFs from UV-B -induced nuclear damage as is evident from Tunnel assay and Acridine Orange/Ethidium Bromide co-staining. Salubrinal, (an eIf2α inhibitor) significantly decreases the DNA damage response in HDFs. P62 silenced HDFs show enhanced DNA damage response and disturbs the tumor suppressor axis PTEN/pAKT towards damage whereas ATG7 silenced HDFs reveal an unexpected consequence by decreasing the UV-B -induced DNA damage compared to UV-B treated HDFs. Together, our results suggest that autophagy is essential in protecting skin cells from UV-B radiation -induced photo-damage and holds great promise in devising it as a suitable therapeutic strategy against skin photo-damage.HighlightsAutophagy is an immediate molecular event induced following exposure of primary HDFs to UV-B –irradiationAutophagy offers pro-survival capacity to HDFs under UV-B induced genotoxic stressAutophagy regulates DNA Damage Response via regulation of oxidative and ER stress in UV-B exposed HDFsRelieving ER stress response offers significant protection to primary HDFs from UV-B by decreasing the DNA damageAutophagy deprivation to HDFs via P62 silencing potentiates UV-B -induced DNA damage responseATG7 silencing in UV-B exposed HDFs unexpectedly alleviates the DNA Damage Response in primary HDFs</jats:sec

Ozone Layer Depletion and Emerging Public Health Concerns - An Update on Epidemiological Perspective of the Ambivalent Effects of Ultraviolet Radiation Exposure

Solar ultraviolet (UV) radiation exposure is the primary etiological agent responsible for developing cutaneous malignancies. Avoiding excessive radiation exposure, especially by high-risk groups, is recommended to prevent UV-induced photo-pathologies. However, optimal sun exposure is essential for the healthy synthesis of about 90% of vitamin D levels in the body. Insufficient exposure to UV-B is linked to vitamin D deficiency in humans. Therefore, optimal sun exposure is necessary for maintaining a normal state of homeostasis in the skin. Humans worldwide face a major existential threat because of climate change which has already shown its effects in several ways. Over the last 4 to 5 decades, increased incidences in skin cancer cases have led international health organizations to develop strong sun protection measures. However, at the same time, a growing concern about vitamin D deficiency is creating a kind of exposure dilemma. Current knowledge of UV exposure to skin outweighs the adverse effects than the beneficial roles it offers to the body, necessitating a correct public health recommendation on optimal sun exposure. Following an appropriate recommendation on optimal sun exposure will lead to positive outcomes in protecting humans against the adverse effects of strict recommendations on sun protection measures. In this short review, we spotlight the ambivalent health effects of UV exposure and how ozone layer depletion has influenced these effects of UVR. Further, our aim remains to explore how to lead towards a balanced recommendation on sun protection measures to prevent the spurt of diseases due to inadequate exposure to UV-B.</jats:p

Integrating DNA damage response and autophagy signalling axis in ultraviolet-B induced skin photo-damage: a positive association in protecting cells against genotoxic stress

Regulation of stress response in cells by autophagy.</p

Molecular basis of skin photoaging and therapeutic interventions by plant-derived natural product ingredients: A comprehensive review

Skin areas exposed to ultraviolet radiation (UV) from sunlight are more prone to photoaging than unexposed areas evidenced by several signs which include skin dryness, irregular pigmentation, lentigines, hyperpigmentation, wrinkling, and decreased elasticity. Plant-based natural product ingredients with therapeutic potential against skin photoaging are gaining more attention. This article aims the reviewing the research work done in exploring the cellular and molecular mechanisms involved in UV-induced skin photoaging, followed by summarizing the mechanistic insights involved in its therapeutics by natural product-based ingredients. In the mechanistic section of the convoluted procedure of photoaging, we described the effect of UV radiation (UVR) on different cellular macromolecules (direct damage) and subsequently, the deleterious consequences of UVR-generated reactive oxygen species (indirect damage) and signaling pathways activated or inhibited by UV induced ROS generation in various cellular pathologies of skin photoaging like inflammation, extracellular matrix degradation, apoptosis, mitochondrial dysfunction, and immune suppression. We also discussed the effect of UV radiation on the adipose tissue, and transient receptor potential cation channel V of photoaging skin. In the past few decades, mechanistic studies performed in this area have deciphered various therapeutic targets, opening avenues for different available therapeutic options against this pathological condition. So the remaining portion of the review deals with various natural product-based therapeutic agents available against skin photodamage