Microbiota Targeted Interventions of Probiotic as an Anti-Ageing Approach: A Review.

With the implementation of modern scientific protocols, the average human lifespan has significantly improved, but age-related problems remain a challenge. With the advent of ageing, there are alterations in gut microbiota and gut barrier functions, weak immune responses, increased oxidative stress, and other age-related disorders. This review has highlighted and discussed the current understanding on the significance of gut microbiota dysbiosis and ageing and its inherent effects against age-related oxidative stress as well as on the gut health and gut-brain axis.

The accuracy of T1-weighted voxel-wise and region-wise metrics for brain age estimation.

Introduction: The brain age score has recently been introduced for robust monitoring of brain morphological alterations throughout the lifespan, prediction of mortality risk, and early detection of neurological disorders.

Methods: We assessed the brain age prediction accuracy of the widely used T1-weighted voxel-wise and region-wise metrics (i.e.

Analyzing differentially expressed genes and pathways of Bex2-deficient mouse lung via RNA-Seq.

is well known for its role in the nervous system, and is associated with neurological disorders, but its role in the lung's physiology is still not reported. To elucidate the functional role of in the lung, we generated a knock-out (KO) mouse model using the CRISPR-Cas9 technology and performed transcriptomic analysis. A total of 652 genes were identified as differentially expressed between and mice, out of which 500 were downregulated, while 152 were upregulated genes.

A bispecific antibody targeting HER2 and PD-L1 inhibits tumor growth with superior efficacy.

Activation of the programmed cell death protein 1 and programmed cell death ligand 1 (PD-1/PD-L1) signaling axis plays important roles in intrinsic or acquired resistance to human epidermal growth factor receptor 2 (HER2)-directed therapies in the clinic. Therefore, therapies simultaneously targeting both HER2 and PD-1/PD-L1 signaling pathways are of great significance. Here, aiming to direct the anti-PD-L1 responses toward HER2-expressing tumor cells, we constructed a humanized bispecific IgG1 subclass antibody targeting both HER2 and PD-L1 (HER2/PD-L1; BsAb), which displayed satisfactory purity, thermostability, and serum stability.

Role of RAGE in obesity-induced adipose tissue inflammation and insulin resistance.

Obesity is known to be associated with adipose tissue inflammation and insulin resistance. Importantly, in obesity, the accumulation of proinflammatory macrophages in adipose tissue correlates with insulin resistance. We hypothesized that the receptor for advanced glycation end products (RAGE) and associated ligands are involved in adipose tissue insulin resistance, and that the activation of the AGE-RAGE axis plays an important role in obesity-associated inflammation.

Gut microbiome colonization and development in neonatal ruminants: Strategies, prospects, and opportunities.

Colonization and development of the gut microbiome is a crucial consideration for optimizing the health and performance of livestock animals. This is mainly attributed to the fact that dietary and management practices greatly influence the gut microbiota, subsequently leading to changes in nutrient utilization and immune response. A favorable microbiome can be implanted through dietary or management interventions of livestock animals, especially during early life.

Effects of an Adenosine A Receptor Antagonist on Striatal Dopamine D2-Type Receptor Availability: A Randomized Control Study Using Positron Emission Tomography.

Altered dopaminergic neurotransmission, especially in the functioning of dopamine D2-type receptors, is considered central to the etiology of a variety of neuropsychiatric disorders. In particular, individuals with substance use disorders have been consistently observed to exhibit lower D2-type receptor availability (quantified as binding potential; BP) using positron emission tomography (PET). Upregulation of D2-type receptor density thus may therefore provide a therapeutic effect for substance use disorders.

Suppression of Colon Tumorigenesis in Mutant Mice by a Novel PDE10 Inhibitor that Reduces Oncogenic β-Catenin.

Previous studies have reported that phosphodiesterase 10A (PDE10) is overexpressed in colon epithelium during early stages of colon tumorigenesis and essential for colon cancer cell growth. Here we describe a novel non-COX inhibitory derivative of the anti-inflammatory drug, sulindac, with selective PDE10 inhibitory activity, ADT 061. ADT 061 potently inhibited the growth of colon cancer cells expressing high levels of PDE10, but not normal colonocytes that do not express PDE10.

Single-subject gray matter networks in temporal lobe epilepsy patients with hippocampal sclerosis.

Objective: Previous studies have demonstrated structural brain network abnormalities in patients with temporal lobe epilepsy (TLE) using cortical thickness or gray matter (GM) volume. However, no studies have applied single-subject GM network analysis. Here, we first applied an analysis of similarity-based single-subject GM networks to individual patients with TLE.

Dl-3-n-Butylphthalide Ameliorates Diabetic Nephropathy by Ameliorating Excessive Fibrosis and Podocyte Apoptosis.

Diabetic nephropathy (DN) is a common diabetes associated complication. Thus, it is important to understand the pathological mechanism of DN and find the appropriate therapeutic strategy for it. Dl-3-n-Butylphthalide (DL-NBP) has anti-inflammatory and antioxidant effects, and been widely used for the treatment of stroke and cardiovascular diseases.

Accurate lateralization and classification of MRI-negative 18F-FDG-PET-positive temporal lobe epilepsy using double inversion recovery and machine-learning.

Objective: The main objective of this study was to determine the ability of double inversion recovery (DIR) data coupled with machine-learning algorithms to distinguish normal individuals from epileptic subjects and to identify the laterality of the focus side in MRI-negative, PET-positive temporal lobe epilepsy (TLE) patients.

Materials And Methods: We used whole-brain DIR data as the input features with which to train a linear support-vector machine model in 63 participants who underwent high-resolution structural MRI and DIR scans. The subjects included 20 left TLE patients, 19 right TLE patients, and 24 healthy controls (HCs).

ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker.

The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.

Long Noncoding RNAs as Emerging Regulators of COVID-19.

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states.

Deletion of SDF-1 or CXCR4 regulates platelet activation linked to glucose metabolism and mitochondrial respiratory reserve.

Stromal cell-derived factor 1 (SDF-1, also known as CXCL12) and its receptor CXCR4 have shown to play a role in the homing and engraftment of hematopoietic stem and progenitor cells. SDF-1 is highly expressed in platelets and involved in thrombosis formation. However, the exact roles of platelet-derived SDF-1 and CXCR4 in platelet activation and mitochondrial function have not been revealed yet.

Novel thiazolidine derivatives as potent selective pro-apoptotic agents.

A series of 2-arylthiazolidine-4-carboxylic acid amide derivatives were synthesized and their cytotoxic activity against three cancer cell lines (PC-3, SKOV3 and MDA-MB231) was evaluated. Various structural modifications were tried including modifications of the length of the amide chain and modifications of the 2-aryl part using disubstituted phenyl and thiophene derivatives. The structure activity relationship was evaluated based on the in vitro biological evaluation against the above mentioned three cancer cell lines.

In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice.

Background: Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.

Methods: We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity.

MG53 inhibits angiogenesis through regulating focal adhesion kinase signalling.

Mitsugumin 53 (MG53), which is expressed predominantly in striated muscle, has been demonstrated to be a myokine/cardiokine secreted from striated muscle under specific conditions. The important roles of MG53 in non-striated muscle tissues have also been examined in multiple disease models. However, no previous study has implicated MG53 in the control of endothelial cell function.

Implication of ferroptosis in aging.

Life is indeed continuously going through the irreversible and inevitable process of aging. The rate of aging process depends on various factors and varies individually. These factors include various environmental stimuli including exposure to toxic chemicals, psychological stress whereas suffering with various illnesses specially the chronic diseases serve as endogenous triggers.

An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies.

Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2.

Gold nanoclusters treat intracellular bacterial infections: Eliminating phagocytic pathogens and regulating cellular immune response.

Intracellular bacterial infection is underlying many serious human disorders, leading to high morbidity and mortality. The development of safe and efficient therapeutic agents is the most effective solutions to combat intracellular bacterial infections. Recently, ultrasmall gold nanoclusters (AuNCs) have emerged as an innovative nanoantibiotics against multidrug-resistant bacterial infections due to their inherent antibacterial activity.

Voxel-based correlation of F-THK5351 accumulation with gray matter structural networks in cognitively normal older adults.

Objective: The aim of this study was to evaluate tau-related structural network metrics derived from gray matter magnetic resonance imaging (MRI) scans in cognitively normal (CN) older adults.

Methods: We recruited 47 amyloid-negative CN older adults (mean age ± standard deviation, 65.0 ± 7.

RAGE: A potential therapeutic target during FGF1 treatment of diabetes-mediated liver injury.

As a serious metabolic disease, diabetes causes series of complications that seriously endanger human health. The liver is a key organ for metabolizing glucose and lipids, which substantially contributes to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Exogenous fibroblast growth factor 1 (FGF1) has a great potential for the treatment of diabetes.

Antagonizing αvβ3 Integrin Improves Ischemia-Mediated Vascular Normalization and Blood Perfusion by Altering Macrophages.

: αVβ3 integrin has been implicated in the physiological processes and pathophysiology of important angiogenesis-related disorders; however, the preclinical and clinical data on integrin αVβ3 antagonists have not demonstrated improved outcomes. Our goal was to test the hypothesis that inhibition of αVβ3 integrin improves blood flow in a mouse hindlimb ischemia model. : In this study, we examined the effect of cilengitide, an αVβ3/αVβ5 integrin-specific RGD-mimetic cyclic peptide, on blood perfusion and angiogenesis after hindlimb ischemia.

HIF-1α Protects Granulosa Cells From Hypoxia-Induced Apoptosis During Follicular Development by Inducing Autophagy.

Owing to the avascular structure of the ovarian follicle, proliferation of granulosa cells (GCs) and development of follicles occur under hypoxia, which is obviously different from the cell survival requirements of most mammalian cells. We hypothesized that autophagy may exert an inhibitory effect on GC apoptosis. To decipher the underlying mechanism, we constructed a rat follicular development model using pregnant mare serum gonadotropin and a cell culture experiment in hypoxic conditions (3% O).