Integrated metagenomic and metabonomic mechanisms for the therapeutic effects of Duhuo Jisheng decoction on intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a prevalent orthopedic condition with lower back pain as the predominant clinical presentation that challenges clinical treatment with few therapeutic options. Duhuo Jisheng Decoction (DHJSD) has been proven effective in the therapy of IVDD, but the precise underlying mechanisms remain not fully elucidated. The current study was designed to test our hypothesis that DHJSD may systematically correct the phenotypic disruption of the gut microbiota and changes in the serum metabolome linked to IVDD.

Astragaloside IV derivative HHQ16 ameliorates infarction-induced hypertrophy and heart failure through degradation of lncRNA4012/9456.

Reversing ventricular remodeling represents a promising treatment for the post-myocardial infarction (MI) heart failure (HF). Here, we report a novel small molecule HHQ16, an optimized derivative of astragaloside IV, which effectively reversed infarction-induced myocardial remodeling and improved cardiac function by directly acting on the cardiomyocyte to reverse hypertrophy. The effect of HHQ16 was associated with a strong inhibition of a newly discovered Egr2-affiliated transcript lnc9456 in the heart.

Shared mechanisms and crosstalk of COVID-19 and osteoporosis via vitamin D.

Recently accumulated evidence implicates a close association of vitamin D (VitD) insufficiency to the incidence and clinical manifestations of the COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Populations with insufficient VitD including patients with osteoporosis are more susceptible to SARS-COV-2 infection and patients with COVID-19 worsened or developed osteoporosis. It is currently unknown, however, whether osteoporosis and COVID-19 are linked by VitD insufficiency.

TMEM16A Plays an Insignificant Role in Myocardium Remodeling but May Promote Angiogenesis of Heart During Pressure-overload.

Cardiac hypertrophy (CH) occurs with an increase in myocardium mass as an adaptive compensation to increased stress. Prolonged CH causes decompensated heart failure (HF). Enhanced angiogenesis by vascular endothelial growth factor (VEGF) is observed in hypertrophied hearts; impaired angiogenesis by angiotensin II (AngII) is observed in failing hearts.

Berberine suppresses colorectal cancer by regulation of Hedgehog signaling pathway activity and gut microbiota.

Background: A growing body of evidence reveals that dysregulation of Hedgehog signaling pathway and dysbiosis of gut microbiota are associated with the pathogenesis of colorectal cancer (CRC). Berberine, a botanical benzylisoquinoline alkaloid, possesses powerful activities against various malignancies including CRC, with the underlying mechanisms to be illuminated.

Purpose: The present study investigated the potencies of berberine on CRC and deciphered the action mechanisms in the context of Hedgehog signaling cascade and gut microbiota.

The cross-talk between PARylation and SUMOylation in C/EBPβ at K134 site participates in pathological cardiac hypertrophy.

Poly(ADP-ribosyl)ation (PARylation) and SUMO modification (SUMOylation) are novel post-translational modifications (PTMs) mainly induced by PARP1 and SUMO1. Growing evidence has revealed that C/EBPβ plays multiple roles in biological processes and participates in cardiovascular diseases. However, the cross-talk between C/EBPβ PARylation and SUMOylation during cardiovascular diseases is unknown.

Blood-brain barrier integrity is the primary target of alcohol abuse.

The effects of long-term alcohol consumptions on cognitive function remain elusive with contradictory results. Whilst it is widely accepted that long-term intoxication can cause cognitive impairment, moderate drinking can improve cognitive function. In reality, many older people and those with chronic medical conditions are long-term alcohol consumers in Asian countries.

CFTR plays an important role in the regulation of vascular resistance and high-fructose/salt-diet induced hypertension in mice.

Background: The pathophysiological roles of cystic fibrosis transmembrane-conductance regulator (CFTR) Cl channels in the regulation of blood pressure (BP) remain controversial. Here we studied the function of CFTR Cl channels in regulation of BP and in the high-fructose-salt-diet (HFSD) induced hypertension in mice.

Methods: The systolic, diastolic and mean BP (SBP, DBP and MBP, respectively) were continuously monitored from unrestricted conscious wild-type (cftr) FVB and CFTR-knockout (cftr) mice (8-week old, male).

Pharmacological and cardiovascular perspectives on the treatment of COVID-19 with chloroquine derivatives.

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and an ongoing severe pandemic. Curative drugs specific for COVID-19 are currently lacking. Chloroquine phosphate and its derivative hydroxychloroquine, which have been used in the treatment and prevention of malaria and autoimmune diseases for decades, were found to inhibit SARS-CoV-2 infection with high potency in vitro and have shown clinical and virologic benefits in COVID-19 patients.

Study of miRNA interactome in active rheumatoid arthritis patients reveals key pathogenic roles of dysbiosis in the infection-immune network.

Objectives: To characterize serum microRNA (miR) and the miR interactome of active RA patients in RA aetiology and pathogenesis.

Methods: The differentially expressed miRs (DEmiRs) in serum of naïve active RA patients (NARAPs, n = 9, into three pools) vs healthy controls (HCs, n = 15, into five pools) were identified with Agilent human miR microarray analysis. Candidate driver genes in epigenetic and pathogenic signalling pathway modules for RA were analysed using miRTarBase and a molecular complex detection algorithm.

Bunge and Panax notoginseng (Burkill) F.H. Chen Formula for Renal Injury in Diabetic Nephropathy- and Evidence for Autophagy Regulation.

Background: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM) with limited treatment options. DN leads to progressive renal failure and accelerates rapidly into end-stage renal disease. Bunge and Panax notoginseng (Burkill) F.

Drinking water temperature affects cognitive function and progression of Alzheimer's disease in a mouse model.

Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer's disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms.

Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation.

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of L., is considered to play a broad role in a variety of biological processes.

Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-κB pathway.

Lower back pain (LBP) is the most common disease in orthopedic clinics world-wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation.

Tumor exosomes: a double-edged sword in cancer therapy.

Tumor cells produce and secrete more nucleic acids, proteins and lipids than normal cells. These molecules are transported in the blood or around the cells in membrane-encapsulated exosomes. Tumor-derived or tumor-associated exosomes (usually 30-100 nm in diameter) contain abundant biological contents resembling those of the parent cells along with signaling messengers for intercellular communication involved in the pathogenesis, development, progression, and metastasis of cancer.

Vascular endothelial growth factor signaling requires glycine to promote angiogenesis.

Peripheral vascular occlusive disease (PVOD) is a common manifestation of atherosclerosis, and it has a high rate of morbidity. Therapeutic angiogenesis would re-establish blood perfusion and rescue ischemic tissue. Vascular endothelial growth factor (VEGF) induces angiogenesis and can potentially be used to treat ischemic diseases, yet in clinical trials VEGF has not fulfilled its full potential with side effects.

Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury.

Background: Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI).

Heart-specific overexpression of the human short CLC-3 chloride channel isoform limits myocardial ischemia-induced ERP and QT prolongation.

Introduction: Ischemia causes myocardial infarction and arrhythmias. Up-regulation of cardiac CLC-3 chloride channels is important for ischemic preconditioning-induced second-window protection against myocardial infarction. But its consequences in ischemia-induced electrical remodeling are still unknown.

Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest.

Background: Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death.