Diabetes and vascular mild cognitive impairment among Chinese ≥50 years: A cross-sectional study with 2020 participants.

Background: With the decline of cognitive function in vascular cognitive impairment, the burden on the family and society will increase. Therefore, early identification of vascular mild cognitive impairment (VaMCI) is crucial. The focus of early identification of VaMCI is on the attention of risk factors.

AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD).

Overexpression of VPS16 correlates with tumor progression and chemoresistance in colorectal cancer.

Vacuolar protein sorting-associated protein 16 homolog (VPS16) is a central member of the VPS core complex (VPS-C) and is reported to function as a tether protein involved in membrane fusion. However, a biological role for VPS16 in tumors remains largely unknown. Herein, we demonstrated that VPS16 was overexpressed in colorectal cancer (CRC) as revealed by qRT-PCR, western blotting, and immunohistochemical analyses.

Anterior gradient 2 increases long-chain fatty acid uptake via stabilizing FABP1 and facilitates lipid accumulation.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a well-established oncogene. Here, we found that mice had a decreased fat mass and hepatic and serum lipid levels compared with their wild-type littermates after fasting, and exhibited reduced high-fat diet (HFD)-induced fat accumulation. Transgenic mice overexpressing AGR2 (/Tg) readily gained fat weight on a HFD but not a normal diet.

The Role of Acupuncture Improving Cognitive Deficits due to Alzheimer's Disease or Vascular Diseases through Regulating Neuroplasticity.

Dementia affects millions of elderly worldwide causing remarkable costs to society, but effective treatment is still lacking. Acupuncture is one of the complementary therapies that has been applied to cognitive deficits such as Alzheimer's disease (AD) and vascular cognitive impairment (VCI), while the underlying mechanisms of its therapeutic efficiency remain elusive. Neuroplasticity is defined as the ability of the nervous system to adapt to internal and external environmental changes, which may support some data to clarify mechanisms how acupuncture improves cognitive impairments.

lncARSR sponges miR-34a-5p to promote colorectal cancer invasion and metastasis via hexokinase-1-mediated glycolysis.

Aerobic glycolysis metabolic reprogramming is one of the most important hallmarks of malignant tumors. Increasing evidence indicates that long non-coding RNAs (lncRNAs) are able to regulate glycolysis metabolic reprogramming and promote cancer progression by functioning as competing endogenous RNAs. lncARSR is a newly identified onco-lncRNA in renal cancer, but its potential role in metastatic colorectal cancer (CRC) remains unclear.

Inactivation of TFEB and NF-B by marchantin M alleviates the chemotherapy-driven pro-tumorigenic senescent secretion.

It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models.

Proteasome inhibition boosts autophagic degradation of ubiquitinated-AGR2 and enhances the antitumor efficiency of bevacizumab.

Anterior gradient 2 (AGR2), a protein belonging to the protein disulfide isomerase (PDI) family, is overexpressed in multiple cancers and promotes angiogenesis to drive cancer progression. The mechanisms controlling AGR2 abundance in cancer remain largely unknown. Here, we observed that AGR2 expression is significantly suppressed by proteasome inhibitor MG132/bortezomib at mRNA and protein levels in lung cancer cells.

Targeting the lysosome by an aminomethylated Riccardin D triggers DNA damage through cathepsin B-mediated degradation of BRCA1.

RD-N, an aminomethylated derivative of riccardin D, is a lysosomotropic agent that can trigger lysosomal membrane permeabilization followed by cathepsin B (CTSB)-dependent apoptosis in prostate cancer (PCa) cells, but the underlying mechanisms remain unknown. Here we show that RD-N treatment drives CTSB translocation from the lysosomes to the nucleus where it promotes DNA damage by suppression of the breast cancer 1 protein (BRCA1). Inhibition of CTSB activity with its specific inhibitors, or by CTSB-targeting siRNA or CTSB with enzyme-negative domain attenuated activation of BRCA1 and DNA damage induced by RD-N.

Terpenoids isolated from Chinese liverworts Lepidozia reptans and their anti-inflammatory activity.

Five new terpenoids (1-5) including two dollabellane-type, one ent-kaurane-type diterpenoids and two sesquiterpenoids were isolated from the Chinese liverwort Lepidozia reptans (L.) Dumort., together with nine known terpenoids (6-14).

STAT3 contributes to lysosomal-mediated cell death in a novel derivative of riccardin D-treated breast cancer cells in association with TFEB.

RDD648, a novel derivative of a natural molecule riccardin D, exhibited potent anticancer activity by targeting lysosomes in vitro and in vivo. Mechanistic studies revealed that RDD648 facilitated STAT3 to translocate into the nucleus, and this activity was involved in lysosome-mediated cell death as evidenced by our finding that inhibition of STAT3 alleviated lysosomal membrane permeabilization. Further investigation indicated that nuclear STAT3 directly interacted with transcription factor TFEB, leading to the partial loss of function of TFEB, which is essential for lysosome turnover.

Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells.

Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively.

Hyper-acetylation contributes to the sensitivity of chemo-resistant prostate cancer cells to histone deacetylase inhibitor Trichostatin A.

Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis.

Comparison of the Mini-Mental State Examination and Montreal Cognitive Assessment executive subtests in detecting post-stroke cognitive impairment.

Aim: The Montreal Cognitive Assessment (MoCA) has been shown to be more sensitive in detecting executive dysfunction than the Mini-Mental State Examination (MMSE). However, it is still not known whether all the MoCA executive subtests contribute to the superior sensitivity. Thus, the present study aimed to determine how much executive abnormality was detected by the MMSE and MoCA executive subtests in a population-based cohort of Chinese post-stroke patients.

Design, synthesis, biological evaluation and molecular modeling study of novel macrocyclic bisbibenzyl analogues as antitubulin agents.

A series of macrocyclic bisbibenzyls with novel skeletons was designed, synthesized, and evaluated for antiproliferative activity against five anthropic cancer cell lines. Among these novel molecules, compound 47 displayed excellent anticancer activity against HeLa, k562, HCC1428, HT29 and PC-3/Doc cell lines, with IC values ranging from of 1.51 μM-5.

Riccardin D-N induces lysosomal membrane permeabilization by inhibiting acid sphingomyelinase and interfering with sphingomyelin metabolism in vivo.

Lysosomes are important targets for anticancer drug discovery. Our previous study showed that Riccardin D-N (RD-N), a natural macrocylic bisbibenzyl derivative produced by Mannich reaction, induced cell death by accumulating in lysosomes. Experiments were performed on human lung squamous cell carcinoma tissue from left inferior lobar bronchus of patient xenografts and H460 cells.

Design, synthesis and biological evaluation of novel macrocyclic bisbibenzyl analogues as tubulin polymerization inhibitors.

A series of novel macrocyclic bisbibenzyl analogues was designed, synthesized, and evaluated for their antiproliferative activity in vitro. All of the compounds were tested in five anthropic cancer cell lines, including a multidrug-resistant phenotype. Among these novel molecules, compounds 88, 92 and 94 displayed excellent anticancer activity against Hela, k562, HCC1428, HT29, and PC-3/Doc cell lines, with average IC50 values ranging from 2.

Jungermannenone A and B induce ROS- and cell cycle-dependent apoptosis in prostate cancer cells in vitro.

Aim: Jungermannenone A and B (JA, JB) are new ent-kaurane diterpenoids isolated from Chinese liverwort Jungermannia fauriana, which show anti-proliferation activities in cancer cells. In this study we investigated the mechanisms underlying the anticancer action of JA and JB in PC3 human prostate cancer cells in vitro.

Methods: A panel of 9 human cancer cell lines was tested.

Metabolic Syndrome and Cognitive Performance Among Chinese ≥50 Years: A Cross-Sectional Study with 3988 Participants.

Background: To date, the relationship between metabolic syndrome (MetS) and cognitive performance has not been well defined. This study aimed to explore the relationship between MetS and cognitive performance among Chinese elderly population.

Methods: A cross-sectional study was performed, with data collected in seven clinical centers from five provinces of Northern China.

ent-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition As Detected in Situ by a Fluorescence Probe.

It is generally accepted that the origin of the cytotoxicity of ent-kaurane diterpenoids is due to the formation of reactive oxygen species (ROS) and that the α,β-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate the isolation of 32 new and 12 known ent-kaurane diterpenoids from two Chinese liverworts. These compounds and three semisynthesized derivatives were screened against human cancer cell lines.

Quantitative study evaluating perception of general public towards role of pharmacist in health care system of Pakistan.

To investigate general public perception towards the role of pharmacist in developing countries' healthcare system was the main aim of this study, which would be the basic foundation for researching the treatment pattern of cognitive disorder after stroke in communities. The study population (sample size = 385) consisted of general public from Islamabad, Faisalabad and Lahore, Pakistan. Main sections of the questionnaire comprised of series of statements pertaining to consumer's perception and experience with the pharmacists.