Discovery of novel berberine derivatives with balanced cholinesterase and prolyl oligopeptidase inhibition profile.

Berberine, a naturally occurring compound, possesses an interesting multipotent pharmacological profile potentially applicable for Alzheimer's disease (AD) treatment. In this study, a series of novel 22 berberine derivatives was developed and tested in vitro. Berberine core was substituted at position 9-O of its aromatic ring region.

MR elastography of the liver: comparison of three measurement methods.

Aim: To analyse the inter- and intra-observer agreement of liver stiffness value (LSV) using three methods with 3 T magnetic resonance elastography (MRE) and to investigate factors related to LSV difference.

Materials And Methods: This retrospective study included 147 patients. Two independent observers measured the LSV using three region of interest (ROI) methods: (1) circular ROI with a radius of 1 cm in the right lobe, (2) largest ROI possible, and (3) average value considering the measurement area.

Comparing Central Pain Processing in Individuals With Non-Traumatic Neck Pain and Healthy Individuals: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis examined the evidence for altered central pain processing in people with nontraumatic neck pain and the relationship among central pain processing, demographics, and pain-related characteristics. Case-control studies reporting measures of altered central pain processing using quantitative sensory testing were reviewed. Standardized mean differences (SMDs) and 95% confidence intervals between people with nontraumatic neck pain and controls were calculated.

Liver X Receptor Alpha Activation Inhibits Autophagy and Lipophagy in Hepatocytes by Dysregulating Autophagy-Related 4B Cysteine Peptidase and Rab-8B, Reducing Mitochondrial Fuel Oxidation.

Background And Aims: Fat accumulation results from increased fat absorption and/or defective fat metabolism. Currently, the lipid-sensing nuclear receptor that controls fat utilization in hepatocytes is elusive. Liver X receptor alpha (LXRα) promotes accumulation of lipids through the induction of several lipogenic genes.

Increasing comorbidities in a South Korea insured population-based cohort of patients with chronic hepatitis B.

Background: It is controversial whether chronic hepatitis B (CHB) patients have more non-liver comorbidities than non-CHB subjects.

Aim: To characterise the demographics, comorbidity and health utilisation of CHB patients in South Korea and compare them to matched controls.

Methods: Using the Health Insurance Review & Assessment Service (HIRA) 2007-2016 database, adult patients with claims for CHB analysed.

MicroRNA-138 targets SOX4 to regulate the proliferation and metastasis of human lung cancer cells.

Purpose: The current study was set with a purpose to assess the regulatory role of micro RNA (miR)-138 in human lung cancer cells with emphasis on the underlying mechanism of action.

Methods: RT-PCR based analysis was employed for gene expression studies. MTT assay was used to determine the proliferation rates of lung cancer cells.

Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer's disease.

A novel series of aromatic esters (1a-1m) related to the Amaryllidaceae alkaloid (AA) haemanthamine were designed, synthesized and tested in vitro with particular emphasis on the treatment of neurodegenerative diseases. Some of the synthesized compounds revealed promising acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory profile. Significant human AChE (hAChE) inhibition was demonstrated by 11-O-(3-nitrobenzoyl)haemanthamine (1j) with ICvalue of 4.

Is It the Twilight of BACE1 Inhibitors?

β-secretase (BACE1) has been regarded as a prime target for the development of amyloid beta (Aβ) lowering drugs in the therapy of Alzheimer´s disease (AD). Although the enzyme was discovered in 1991 and helped to formulate the Aβ hypothesis as one of the very important features of AD etiopathogenesis, progress in AD treatment utilizing BACE1 inhibitors has remained limited. Moreover, in the last years, major pharmaceutical companies have discontinued clinical trials of five BACE1 inhibitors that had been strongly perceived as prospective.

Sequential Combination of FIB-4 Followed by M2BPGi Enhanced Diagnostic Performance for Advanced Hepatic Fibrosis in an Average Risk Population.

The fibrosis-4 (FIB-4) index is the most widely used estimated formula to screen for advanced hepatic fibrosis; however, it has a considerable intermediate zone. Here, we propose an algorithm to reduce the intermediate zone and improve the diagnostic performance of screening for advanced liver fibrosis by incorporating Mac-2-binding protein glycan isomer (M2BPGi) into a FIB-4 based screening strategy in an average risk group. Four-hundred eighty-eight healthy and chronic liver disease subjects were analyzed using a 1:1 propensity score matched for age and sex.

Introduction of the Menaquinone Biosynthetic Pathway into and Synthesis of Menaquinone for Incorporation into Heterologously Expressed Integral Membrane Proteins.

Quinones are redox-active molecules that transport electrons and protons in organelles and cell membranes during respiration and photosynthesis. In addition to the fundamental importance of these processes in supporting life, there has been considerable interest in exploiting their mechanisms for diverse applications ranging from medical advances to innovative biotechnologies. Such applications include novel treatments to target pathogenic bacterial infections and fabricating biohybrid solar cells as an alternative renewable energy source.

Hepatic stellate cell-specific knockout of transcriptional intermediary factor 1γ aggravates liver fibrosis.

Transforming growth factor β (TGFβ) is a crucial factor in fibrosis, and transcriptional intermediary factor 1γ (TIF1γ) is a negative regulator of the TGFβ pathway; however, its role in liver fibrosis is unknown. In this study, mesenchymal stem cells derived from human embryonic stem cells (hE-MSCs) that secrete hepatocyte growth factor (HGF) were used to observe the repair of thioacetamide (TAA)-induced liver fibrosis. Our results showed that TIF1γ was significantly decreased in LX2 cells when exposed to TGFβ1.

Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2).

Purpose: Lianhuaqingwen (LH) as traditional Chinese medicine (TCM) formula has been used to treat influenza and exerted broad-spectrum antiviral effects on a series of influenza viruses and immune regulatory effects Ding et al. (2017). The goal of this study is to demonstrate the antiviral activity of LH against the novel SARS-CoV-2 virus and its potential effect in regulating host immune response.

Benzothiazolyl Ureas are Low Micromolar and Uncompetitive Inhibitors of 17β-HSD10 with Implications to Alzheimer's Disease Treatment.

Human 17β-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g.

Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation.

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp.

A case report: white cord syndrome following anterior cervical discectomy and fusion: importance of prompt diagnosis and treatment.

Background: Objective: White cord syndrome is extremely rare and search of the literature has revealed very few cases. Postoperative MR scan revealed hyperintense intrinsic cord signal changes within cord ischemia and edema. It is thought to be caused by reperfusion injury of the spinal cord.

Establishment of patient-derived three-dimensional organoid culture in renal cell carcinoma.

Purpose: Renal cell carcinoma is a heterogeneous kidney cancer, and over 403,000 cases were reported worldwide in 2018. Current methods for studying renal cell carcinoma are limited to two-dimensional (2D) culture of primary cell lines and patient-derived xenograft models. Numerous studies have suggested that 2D culture poorly represents the diversity, heterogeneity, and drug-resistance of primary tumors.

No Difference in Incidence of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection Treated With Entecavir vs Tenofovir.

Background & Aims: Studies to evaluate risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection treated with the nucelos(t)ide analogues entecavir or tenofovir have produced contradictory results. These differences are likely to be the result of censored data, insufficient observation periods, and different observation periods for patients treated with different drugs. We aimed to compare the incidence of HCC development between patients treated with oral entecavir or tenofovir and followed up for the same time periods.

Modelling NAFLD disease burden in four Asian regions-2019-2030.

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) account for an increasing proportion of liver disease in the Asia-Pacific region. Many areas in the region are experiencing epidemics of metabolic syndrome among rapidly ageing populations.

Aims: To estimate using modelling the growth in NAFLD populations, including cases with significant fibrosis that are most likely to experience advanced liver disease and related mortality.

A Longitudinal Evaluation of Risk Factors and Interactions for the Development of Nonspecific Neck Pain in Office Workers in Two Cultures.

Objective: To identify risk factors for the development of interfering neck pain in office workers including an examination of the interaction effects between potential risk factors.

Background: The 1-year incidence of neck pain in office workers is reported as the highest of all occupations. Identifying risk factors for the development of neck pain in office workers is therefore a priority to direct prevention strategies.

QSEN Transcends Cultures: Teaching Quality and Safety Education in China.

There has been increasing focus on improving the quality and safety of health care globally. Understanding that the health of one nation impacts others worldwide drives initiatives for collaboration to improve the health of all. In this, the Year of the Nurse and Midwife as designated by the World Health Organization, The Quality and Safety Education for Nurses (QSEN) Competencies provide structure that transcends culture for framing the nursing role to contribute to improving patient safety and the quality of care delivery internationally.

Recurrent Coronary Artery Vasospasm in a Patient with Hepatocellular Carcinoma Treated with Sorafenib: a Case Report and Literature Review.

Tyrosine kinase inhibitors are widely used as targeted treatments for various malignancies. Sorafenib is an orally active tyrosine kinase inhibitor that blocks the signaling pathways of several growth factors. Its use is approved for various malignancies such as unresectable hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumors.