Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B

xlomafota13 shared this article with you from Inoreader Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1325. doi: 10.3892/etm.2021.10760. Epub 2021 Sep 20. ABSTRACT Tenofovir alafenamide fumarate (TAF) is a first-line drug for the antiviral treatment of patients with chronic hepatitis B (CHB) in China. In the present study, the efficacy and renal safety of TAF were evaluated in treatment-naive patients with CHB. Patients with CHB who had not been previously treated with nucleoside analogues (NAs) were recruited before TAF treatment was initiated. Changes in the levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were analyzed at 24 and 48 weeks using immunoassays. In addition, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were analyzed using transient elastography, while alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels, calcium (Ca) and inorga nic phosphorus (IP) levels were measured using biochemistry assay. In addition, the estimated glomerular filtration rate (eGFR) was calculated. After 48 weeks, the ALT normalization rate was 95.24% (40/42), the complete virological response (HBV DNA <20 IU/ml) rate was 69.05% (29/42) and the HBeAg seroconversion rate was 8.57% (3/35). The levels of HBV DNA and HBsAg were significantly decreased from the baseline at 5.49±1.95 to 1.26±0.66 log10 IU/ml and from 3.59±0.81 to 3.32±0.55 log10 IU/ml after 48 weeks of treatment, respectively. Compared with that in the baseline measurements, LSM at 48 weeks was significantly decreased from 13.00±8.15 to 8.66±4.45 kPa. No significant differences were observed in the TG, TC, LDL-C, CAP, eGFR, Ca and IP measurements. According to the baseline ALT levels, patients were divided into group A [ALT ≤1 x upper limit of normal (ULN); ULN=50 U/l; n=21], group B (1 x ULN < ALT <2 x ULN; n=22) and group C (ALT ≥2 x ULN; n=18). A significant decrease in HBsAg levels was observed in group B (3.63±0.68 vs. 3.53±0.63 log10 IU/ml) and group C (4.15±0.57 vs. 3.66±0.48 log10 IU/ml) at 24 weeks compared with the baseline. In conclusion, TAF was found to be effective and safe in NA treatment-naive patients with CHB. Moreover, the higher the ALT levels, the more prominent the curative effect from TAF treatment. Therefore, NA treatment-naive CHB patients could benefit from TAF treatment in real world. PMID:34630679 | PMC:PMC8495544 | DOI:10.3892/etm.2021.10760 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Research progress on evodiamine, a bioactive alkaloid of Evodiae fructus: Focus on its anti-cancer activity and bioavailability (Review)

xlomafota13 shared this article with you from Inoreader Research progress on evodiamine, a bioactive alkaloid of <em>Evodiae fructus</em>: Focus on its anti-cancer activity and bioavailability (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1327. doi: 10.3892/etm.2021.10762. Epub 2021 Sep 20. ABSTRACT Evodiae fructus (Wu-Zhu-Yu in Chinese) can be isolated from the dried, unripe fruits of Tetradium ruticarpum and is a well-known traditional Chinese medicine that is applied extensively in China, Japan and Korea. Evodiae fructus has been traditionally used to treat headaches, abdominal pain and menorrhalgia. In addition, it is widely used as a dietary supplement to provide carboxylic acids, essential oils and flavonoids. Evodiamine (EVO) is one of the major bioactive components contained within Evodiae fructus and is considered to be a potential candidate anti-cancer agent. EVO has been reported to exert anti-cancer effects by inhibiting cell proliferation, invasion and metastasis, whilst inducing apoptosis in numerous types of cancer cells. However, EVO is susceptible to metabolism and may inhibit the activities of me tabolizing enzymes, such as cytochrome P450. Clinical application of EVO in the treatment of cancers may prove difficult due to poor bioavailability and potential toxicity due to metabolism. Currently, novel drug carriers involving the use of solid dispersion techniques, phospholipids and nanocomplexes to deliver EVO to improve its bioavailability and mitigate side effects have been tested. The present review aims to summarize the reported anti-cancer effects of EVO whilst discussing the pharmacokinetic behaviors, characteristics and effective delivery systems of EVO. PMID:34630681 | PMC:PMC8495584 | DOI:10.3892/etm.2021.10762 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Yiqi Huoxue preserves heart function by upregulating the Sigma-1 receptor in rats with myocardial infarction

xlomafota13 shared this article with you from Inoreader Yiqi Huoxue preserves heart function by upregulating the Sigma-1 receptor in rats with myocardial infarction Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1308. doi: 10.3892/etm.2021.10743. Epub 2021 Sep 16. ABSTRACT Yiqi Huoxue (YQHX) is widely used in traditional Chinese medical practice due to its reported cardioprotective effects. The aim of the present study was to investigate the mechanism underlying these effects of YQHX via the regulation of the Sigma-1 receptor. The Sigma-1 receptor is a chaperone protein located on the mitochondrion-associated endoplasmic reticulum (ER) membrane. It serves an important role in heart function by regulating intracellular Ca2+ homeostasis and enhancing cellular bioenergetics. In the present study, male Sprague Dawley rats with myocardial infarction (MI)-induced heart failure were used. MI rats were administered different treatments, including normal saline, YQHX and fluvoxamine, an agonist of the Sigma-1 receptor. Following four weeks of treatment, YQHX was revealed to improve heart function and attenuate my ocardial hypertrophy in MI rats. Additionally, YQHX increased the ATP content and improved the mitochondrial ultrastructure in the heart tissues of MI rats in comparison with acontrol. Treatment was revealed to attenuate the decreased expression of the Sigma-1 receptor and increase the expression of inositol triphosphate type 2 receptors (IP3R2) in MI rats. By exposing H9c2 cells to angiotensin II (Ang II), YQHX prevented cell hypertrophy and normalized the decreased ATP content. However, these positive effects were partially inhibited when the Sigma-1 receptor was knocked down via small interfering RNA transfection. The results of the present study suggested that the Sigma-1 receptor serves an important role in the cardioprotective efficacy of YQHX by increasing ATP content and attenuating cardiomyocyte hypertrophy. PMID:34630662 | PMC:PMC8461621 | DOI:10.3892/etm.2021.10743 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Skin anomalies in acromegalic patients (Review of the practical aspects)

xlomafota13 shared this article with you from Inoreader Skin anomalies in acromegalic patients (Review of the practical aspects) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1330. doi: 10.3892/etm.2021.10765. Epub 2021 Sep 20. ABSTRACT Acromegaly is a hormonal disorder which occurs as the result of growth hormone (GH) and insulin growth factor 1 (IGF-1) over-secretion; both hormones are related to skin anomalies. The skin acts as a large endocrine organ, hosting GH receptors in every cell while IGF-1 receptors are expressed only in keratinocytes. This review is a literature review of skin anomalies found in acromegaly, either related to the disease itself or associated with related complications such as secondary diabetes mellitus, or involving associated conditions such as genetic syndromes. The following clinical points are mentioned as follows. Excessive skin and enlargement of soft tissue are due to glycosaminoglycan deposits, edema, and hyperhidrosis (mostly facial and acral). Acanthosis nigricans, a body fold dermatosis associated with insulin resistance, involves local o r diffuse hyperkeratotic plaques with or without hyperpigmentation, caused by growth factors including GH/IGF-1. Other findings include cherry angiomas (due to the effects of lipid anomalies on small vessels); oily skin features with keratosis, epidermoid cysts, crochordons, pseudo-acanthosis nigricans; a potentially higher prevalence of varicose veins and psoriasis; low level of evidence for basal cell carcinoma, respective hidroadenitis suppurativa has been noted. In addition, complicated uncontrolled secondary diabetes mellitus (DM) may result in necrobiosis lipoidica diabeticorum, diabetic dermopathy, skin bacterial infections, dermatological complications of diabetic neuropathy, and nephropathy. Finally, associated hereditary syndromes may cause collagenomas, fibromas/angiofibromas, lipomas in multiple endocrine neoplasia type 1 (MEN1) syndrome; café-au-lait macules, early onset neurofibromas, juvenile xanthogranuloma (involving non-Langerhans cell histiocytes), and intertrigi nous freckling in neurofibromatosis type 1. Clinical findings are differentiated from pseudo-acromegaly such as pachydermoperiostosis. Iatrogenic rash, lipodystrophy (lipoatrophy with/without lipohypertrophy) are rarely reported after pegvisomant/somatostatin analogues or after insulin use for DM. Experiments using human cell lines have shown that GH/IGF-1 over-secretion are prone to epithelial-to-mesenchymal transition (EMT) in melanoma. In non-acromegalic subjects, the exact role of GH/IGF-1 in skin tumorigenesis is yet to be determined. Skin in acromegaly speaks for itself, either as the first step of disease identification or as a complication or part of a complex syndromic context. PMID:34630684 | PMC:PMC8495547 | DOI:10.3892/etm.2021.10765 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metformin attenuates H2O2-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

xlomafota13 shared this article with you from Inoreader Metformin attenuates H<sub>2</sub>O<sub>2</sub>-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1316. doi: 10.3892/etm.2021.10751. Epub 2021 Sep 17. ABSTRACT Osteoporosis is a common metabolic disease that has a high incidence in postmenopausal women. Studies have indicated that oxidative damage plays an important role in the development of postmenopausal osteoporosis. Metformin has been showed to have the ability to relieve excessive oxidation. The aim of the present was to determine the therapeutic effect and potential mechanism of metformin in postmenopausal osteoporosis. Oxidative damage was stimulated in vitro by the addition of H2O2 to MC3T3-E1 cells and a mouse menopausal model was also constructed. Cell viability and flow cytometry experiments were performed to determine the effects of H2O2 and metformin treatment on apoptosis. Mitochondrial membrane potential was tested by JC-1 assays. Western blotting was used to detect the expression of mit ochondrial apoptosis markers and antioxidant enzymes. Small interfering RNA was used to knockdown sirtuin3 (SIRT3), which was verified at the mRNA and protein levels. Bilateral ovariectomy was used to prepare menopausal mice, which were analyzed using micro-computed tomography. The results indicated that metformin is able to repair mitochondrial damage and inhibit the apoptosis of osteoblasts induced by H2O2, and also reverse bone mass loss in ovariectomized mice. Western blotting results demonstrated the involvement of SIRT3 in the production of antioxidant enzymes that are essential in protecting against mitochondrial injury. In addition, experiments with SIRT3 knockdown indicated that metformin reverses H2O2-induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway. The results of the present reveal the pathogenesis of oxidative damage and the therapeutic effect of metformin in postmenopausal osteopor osis. They also suggest that SIRT3 is a potential drug target in the treatment of osteoporosis, with metformin being a candidate drug for modification and/or clinical application. PMID:34630670 | PMC:PMC8495548 | DOI:10.3892/etm.2021.10751 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence-accelerated mouse prone 8 mice

xlomafota13 shared this article with you from Inoreader An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence-accelerated mouse prone 8 mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1320. doi: 10.3892/etm.2021.10755. Epub 2021 Sep 20. ABSTRACT A previous study demonstrated that middle-aged (5-6 months of age) senescence-accelerated mouse prone 8 (SAMP8) mice can be used as animal models of mild cognitive impairment (MCI). An enriched environment (EE) can mitigate cognitive decline and decrease the pathological changes associated with various neurodegenerative diseases. In the present study, the learning-memory abilities of SAMP8 mice during the MCI phase (5 months of age) was evaluated and neuropathological changes in the hippocampus were examined after the mice were exposed to an EE for 60 days. In the Morris water maze test, EE-exposed mice demonstrated significantly decreased escape latency and increased time spent in the target quadrant and number of platform crossings compared with control mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining showed that EE-exposed mice had reduced neuronal apoptosis and increased number of surviving neurons compared with control mice. Golgi staining, transmission electron microscopy, and immunohistochemical staining demonstrated that EE-exposed mice exhibited increased dendritic spine densities among secondary and tertiary apical dendrites; increases in synaptic numerical density, synaptic surface density, and expression of synaptophysin; and reduced deposition of amyloid-β (Aβ) and expression of amyloid-precursor protein (APP) in the hippocampal CA1 region compared with control mice. These results demonstrate that EE exposure effectively decreases neuronal loss and regulates neuronal synaptic plasticity by reducing the expression of APP and the deposition of Aβ in the hippocampal CA1 region, thereby mitigating cognitive decline in SAMP8 mice during the MCI phase and delaying the progression from MCI to Alzheimer's disease. PMID:34630674 | PMC:PMC8495563 | DOI:10.3892/etm.2021.10755 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of Psoralea corylifolia L. seed extract on AGEs-induced cell proliferation and fibrotic factor expression in mesangial cells

xlomafota13 shared this article with you from Inoreader Effects of <em>Psoralea corylifolia</em> L. seed extract on AGEs-induced cell proliferation and fibrotic factor expression in mesangial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1332. doi: 10.3892/etm.2021.10767. Epub 2021 Sep 20. ABSTRACT Diabetic nephropathy is a microvascular complication of diabetes that is characterized by mesangial expansion and thickening of the glomerular basement membrane. The production of advanced glycation end products (AGEs) increases in diabetic patients. Activation of the receptor of AGE (RAGE) signaling pathway induces mesangial expansion via the reactive oxygen species (ROS)-mediated production of pro-inflammatory and extracellular matrix molecules. The Psoralea corylifolia L. seed (PCS) is a widely used herbal medicine with various biological activities. The current study investigated the effect of PCS extract on mesangial cell proliferation and the RAGE signaling pathway in SV40 MES 13 cells. SV40 MES 13 cells were harvested after treatment with various concentrations of PCS extract at 10 µg/ml AGEs for 24 h. The results revealed that the PCS extract inhibited AGEs-induced mesangial cell proliferation and cyclin protein expression in a concentration-dependent manner. In addition, the AGEs-induced expression of fibrotic factors, such as transforming growth factor β, fibronectin and collagen, was reduced in mesangial cells after exposure to the PCS extract. The PCS extract also reduced RAGE expression and inhibited the expression of its downstream signaling pathways, such as NADPH oxidase, intracellular ROS and phospho-NF-κB. In conclusion, the data suggested that the PCS extract attenuated AGEs-induced renal mesangial cell proliferation and fibrosis via the suppression of oxidative stress and the downregulation of inflammatory and fibrotic factor expression. PMID:34630686 | PMC:PMC8495585 | DOI:10.3892/etm.2021.10767 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.