Perioperative Antiviral Treatment Facilitate the Postoperative Recovery for Patients with HBV Related to Hepatocellular Carcinoma

Objective: This study aimed to determine whether perioperative antiviral treatment is facilitate for patients with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) and Child-Pugh grade A cirrhosis in perioperative recovery of liver function and HBV activation. Methods: The study included 115 patients with HBV-related HCC and Child-Pugh grade A cirrhosis who underwent resection. Patients were prospectively assigned to a preoperative antiviral treatment group (n = 51) or postoperative antiviral treatment group (n = 52); twelve patients who had not received antiviral treatment before and after surgery were designated a non-treatment group (n = 12). HBV reactivation during a month after the operation was defined as a HBV DNA value tenfold over preoperative values. Postoperative liver dysfunction was defined as prothrombin activity <50% and serum bilirubin >50 mmol/L on postoperative day 5. Results: Postoperatively, liver dysfunction was present in 1 of 51 (1.96%) patients who received preoperative antiviral therapy, 1 of 52 (1.92%) who received postoperative therapy, and 3 of 12 (25%) who received no antiviral therapy. HBV reactivation postoperatively occurred at similar rates. Conclusions: Preoperative and postoperative antiviral treatment of patients with Child-Pugh grade A cirrhosis and high levels of HBV DNA undergoing hepatic resection for HCC are both facilitate in preventing perioperative liver dysfunction and reactivation of HBV. Thus, in this population with high levels of HBV DNA, perioperative antiviral treatment is important

Vertically-aligned Mn(OH)2 nanosheet films for flexible all-solid-state electrochemical supercapacitors

The arrangement of the electrode materials is a significant contributor for constructing high performance supercapacitor. Here, vertically-aligned Mn(OH)2 nanosheet thin films were synthesized by cathodic electrodeposition technique on flexible Au coated polyethylene terephthalate substrates. Morphologies, microstructures, chemical compositions and valence state of the nanosheet films were characterized systematically. It shows that the nanosheets arranged vertically to the substrate, forming a porous nanowall structures and creating large open framework, which greatly facilitate the adsorption or diffusion of electrolyte ions for faradaic redox reaction. Electrochemical tests of the films show the specific capacitance as high as 240.2 F g−1 at 1.0 A g−1. The films were employed to assemble symmetric all-solid-state supercapacitors with LiCl/PVA gel severed as solid electrolyte. The solid devices exhibit high volumetric capacitance of 39.3 mF cm−3 at the current density 0.3 mA cm−3 with robust cycling stability. The superior performance is attributed to the vertically-aligned configuration

Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy

The emergence of immunotherapy has revolutionized the treatment landscape for various types of cancer. Nevertheless, lung cancer remains one of the leading causes of cancer-related mortality worldwide due to the development of resistance in most patients. As one of the most abundant groups of immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play crucial and complex roles in the development of lung cancer, including the regulation of immunosuppressive TME remodeling, metabolic reprogramming, neoangiogenesis, metastasis, and promotion of tumoral neurogenesis. Hence, relevant strategies for lung cancer therapy, such as inhibition of macrophage recruitment, TAM reprograming, depletion of TAMs, and engineering of TAMs for drug delivery, have been developed. Based on the satisfactory treatment effect of TAM-targeted therapy, recent studies also investigated its synergistic effect with current therapies for lung cancer, including immunotherapy, radiotherapy, chemotherapy, anti-epidermal growth factor receptor (anti-EGFR) treatment, or photodynamic therapy. Thus, in this article, we summarized the key mechanisms of TAMs contributing to lung cancer progression and elaborated on the novel therapeutic strategies against TAMs. We also discussed the therapeutic potential of TAM targeting as adjuvant therapy in the current treatment of lung cancer, particularly highlighting the TAM-centered strategies for improving the efficacy of anti-programmed cell death-1/programmed cell death-ligand 1 (anti-PD-1/PD-L1) treatment

Serum bilirubin is negatively associated with white blood cell count

OBJECTIVE: Bilirubin is considered an important antioxidant, anti-inflammatory factor and immunomodulator. The current investigation aimed to explore the association between bilirubin and white blood cell (WBC) count in a large Chinese cohort. METHODS: A total of 61091 participants (29259 males, 31832 females) were recruited from a Chinese tertiary hospital. Data were sorted by sex, and the association between bilirubin and WBC count was analyzed after dividing bilirubin levels into quartiles. RESULTS: Most parameters (including age, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, uric acid, triglycerides and WBC count) were significantly higher in men than in women. Bilirubin displayed significant negative relationships with most other measured variables. Linear logistic regression analysis further indicated their negative relationships. Females showed a significantly higher frequency of leucopenia than males. Significant associations of leucopenia with high bilirubin quartiles were shown in binary logistic regression models for both sexes, with a much closer association in men than in women. For instance, for men with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.600-times higher than that of men with values in quartile 1. For women with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.135-times higher than that of women with values in quartile 1. CONCLUSION: Bilirubin is negatively related to WBC count. Significant associations exist between leucopenia and high bilirubin quartiles, and these associations are more obvious in men than in women

Multitarget-Directed Gallium(III) Tris(acyl-pyrazolonate) Complexes Induce Ferroptosis in Cancer Cells via Dysregulation of Cell Redox Homeostasis and Inhibition of the Mevalonate Pathway

A series of Ga(Q(n))(3) coordination compounds have been synthesized, where HQ(n) is 1-phenyl-3-methyl-4-RC(=O)-pyrazolo-5-one. The complexes have been characterized through analytical data, NMR and IR spectroscopy, ESI mass spectrometry, elemental analysis, X-ray crystallography, and density functional theory (DFT) studies. Cytotoxic activity against a panel of human cancer cell lines was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with interesting results in terms of both cell line selectivity and toxicity values compared with cisplatin. The mechanism of action was explored by spectrophotometric, fluorometric, chromatographic, immunometric, and cytofluorimetric assays, SPR biosensor binding studies, and cell-based experiments. Cell treatment with gallium(III) complexes promoted several cell death triggering signals (accumulation of p27, PCNA, PARP fragments, activation of the caspase cascade, and inhibition of the mevalonate pathway) and induced changes in cell redox homeostasis (decreased levels of GSH/GPX4 and NADP(H), increased reactive oxygen species (ROS) and 4-hydroxynonenal (HNE), mitochondrial damage, and increased activity of CPR and CcO), identifying ferroptosis as the mechanism responsible for cancer cell death

Egy 14. századi új Salamon: V. (Bölcs) Károly francia király

The result of in-hospital all mortality (P < 0.001; RR 3.23; 95% CI 2.28–4.57). (DOCX 54 kb

SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells

<p>Abstract</p> <p>Background</p> <p>Nanometer silicon dioxide (nano-SiO₂) has a wide variety of applications in material sciences, engineering and medicine; however, the potential cell biological and proteomic effects of nano-SiO₂exposure and the toxic mechanisms remain far from clear.</p> <p>Results</p> <p>Here, we evaluated the effects of amorphous nano-SiO₂(15-nm, 30-nm SiO₂). on cellular viability, cell cycle, apoptosis and protein expression in HaCaT cells by using biochemical and morphological analysis, two-dimensional differential gel electrophoresis (2D-DIGE) as well as mass spectrometry (MS). We found that the cellular viability of HaCaT cells was significantly decreased in a dose-dependent manner after the treatment of nano-SiO₂and micro-sized SiO₂particles. The IC₅₀value (50% concentration of inhibition) was associated with the size of SiO₂particles. Exposure to nano-SiO₂and micro-sized SiO₂particles also induced apoptosis in HaCaT cells in a dose-dependent manner. Furthermore, the smaller SiO₂particle size was, the higher apoptotic rate the cells underwent. The proteomic analysis revealed that 16 differentially expressed proteins were induced by SiO₂exposure, and that the expression levels of the differentially expressed proteins were associated with the particle size. The 16 proteins were identified by MALDI-TOF-TOF-MS analysis and could be classified into 5 categories according to their functions. They include oxidative stress-associated proteins; cytoskeleton-associated proteins; molecular chaperones; energy metabolism-associated proteins; apoptosis and tumor-associated proteins.</p> <p>Conclusions</p> <p>These results showed that nano-SiO₂exposure exerted toxic effects and altered protein expression in HaCaT cells. The data indicated the alterations of the proteins, such as the proteins associated with oxidative stress and apoptosis, could be involved in the toxic mechanisms of nano-SiO₂exposure.</p

Evolution of Cerebral Ischemia Assessed by Amide Proton Transfer-Weighted MRI

In today’s stressful world, psychopathy (especially anxiety) is receiving increased importance. Most of the drugs used to treat this disease have several side effects. Medicinal plants derived from natural products have fewer side effects and can be used in the treatment of this disease. The aim of this study was to evaluate the effect of the hydroalcoholic extract of Rosmarinus officinalis L. on anxiety in mice. In this experimental study, 50 male mice were randomly divided into 5 groups. To evaluate anxiety, the Elevated Plus Maze test was performed. The control group received normal saline, the positive control group received diazepam (1 mg/kg) as intraperitoneal injection, and the experimental groups received doses of 100, 200, and 400 mg/kg body weight of rosemary extract. The data were analyzed using SPSS 15 and ANOVA statistical tests. The results show that rosemary extract dose-dependently increases the mice spending time and the entries number of mice in plus maze open arms (indicating less stress). This effect at a dose of 400 mg/kg was similar to diazepam, which, in comparison to the control group, was statistically significant ( P .05). On the other hand, the rosemary extract, similar to the standard drug diazepam, showed an anti-anxiety effect. This effect is probably due to the presence of flavonoids in this plant and their antioxidant property

Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis

BackgroundVariants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM).MethodA systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis.ResultsA total of 30 related eligible studies about OCT genes (SLC22A1, SLC22A2, and SLC22A3) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in SLC22A1, SLC22A2, and SLC22A3, respectively, were investigated. Meta-analysis showed that the SLC22A1 rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = −0.45 [−0.73–−0.18]; p = 0.001). The GG genotype of the SLC22A1 rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = −0.60 [−1.04–0.16], p = 0.007; GG vs. AG: −0.45 [−0.67–0.20], p &lt; 0.001). No statistical association was found between the remaining variants and metformin response and intolerance.ConclusionSLC22A1 rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes

Amide Proton Transfer MRI Signal as a Surrogate Biomarker of Ischemic Stroke Recovery in Patients With Supportive Treatment

Background: Amide proton transfer (APT) MR imaging has shown great potential in the evaluation of stroke severity because of its sensitivity to acid environments. However, this promising MRI technique has not been used to assess treatment efficacy with regard to stroke recovery.Purpose: To assess the therapeutic effect of supportive treatment in ischemic stroke patients using the pH-sensitive APT MRI technique.Material and Methods: Forty-three ischemic stroke patients at an early stage were recruited and scanned with conventional and APT MRI sequences at 3T before treatment. After treatment, 26 patients underwent a follow-up MRI scan (one to three times on different days). The magnetization-transfer-ratio asymmetry at 3.5 ppm, usually called the APT-weighted (APTW) signal, was measured. The APTW signal changes following treatment were analyzed.Results: Baseline APTW signal intensities in the infarcted lesions inversely correlated with baseline stroke severity. Lesion APTW values gradually increased with time in 24 cases (92.3%) with a follow-up MRI scan, showing clinical symptom improvements. Two cases (7.7%) showed further decreased APTW signal in the follow-up scan, accompanied by clinical symptom aggravation. Compared to the baseline, significant APTW signal increases were found for all post-treatment patients (efficacious), whether based on post-treatment or on stroke onset times. The increase in APTW signal in the ischemic stroke lesion after treatment was associated with an improvement in clinical symptoms.Conclusion: The APTW signal would be a useful imaging biomarker by which to assess the therapeutic efficacy of ischemic stroke treatment