Deficiency of interleukin-1 receptor antagonist in mice differentially affects bone properties under different genomic backgrounds.

When IL-1 receptor antagonist (IL-1rn) is knocked out, mice have shown strain background dependent and major QTL regulated susceptibility to spontaneously inflammatory arthritis disease (SAD). The impact on bone properties resulting from the interactions of IL-1rn, genomic background strains, and the QTL locus, is unknown. Bone properties in the four specifically bred mouse strains with mutation of IL-1rn and variations in genomic components were investigated with high-resolution MicroCT and genomic analytical tools.

A Perspective on Evaluating Life Stage Differences in Drug Dosages for Drug Labeling and Instructions.

Drug labeling and instructions provide essential information for patients regarding the usage of drugs. Instructions for the dosage of drug usage are critical for the effectiveness of the drug and the safety of patients. The dosage of many drugs varies depending on the patient's age.

From Reactive to Proactive - The Future Life Design to Promote Health and Extend the Human Lifespan.

Disease treatment and prevention have improved the human lifespan. Current studies on aging, such as the biological clock and senolytic drugs have focused on the medical treatments of various disorders and health maintenance. However, to efficiently extend the human lifespan to its theoretical maximum, medicine can take a further proactive approach and identify the inapparent disorders that affect the gestation, body growth, and reproductive stages of the so-called "healthy" population.

Kynurenine acts as a signaling molecule to attenuate pulmonary fibrosis by enhancing the AHR-PTEN axis.

Introduction: Pulmonary fibrosis (PF) is a fatal fibrotic lung disease without any options to halt disease progression. Feasible evidence suggests that aberrant metabolism of amino acids may play a role in the pathoetiology of PF. However, the exact impact of kynurenine (Kyn), a metabolite derived from tryptophan (Trp) on PF is yet to be addressed.

Optimizing oral immune tolerance to Type II collagen in patients with rheumatoid arthritis: The importance of dose, interfering medication and genetics.

Objectives: Oral immune tolerance (OT) is a complex process with unknown genetic regulation. Our aim is to explore possible genetic control of OT in patients with rheumatoid arthritis (RA).

Methods: RA patients with increased interferon γ production invitro when their isolated peripheral blood mononuclear cells (PBMC) were cultured with type II bovine collagen α1 chain [α1 (II)] were enrolled in this study and were randomly assigned to the "Low dose" type II collagen (CII) group (30 µg/day for 10 weeks, followed by 50 µg/day for 10 weeks, followed by 70 µg/day for 10 weeks) or "High dose" CII group (90 µg/day for 10 weeks, followed by 110 µg/day for 10 weeks, followed by 130 µg/day for 10 weeks).

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28.

It is time to explore the impact of length of gestation and fetal health on the human lifespan.

A recently proposed principal law of lifespan (PLOSP) proposes to extend the whole human lifespan by elongating different life stages. As the preborn stage of a human being, gestation is the foundation for the healthy development of the human body. The antagonistic pleiotropy (AP) theory of aging states that there is a trade-off between early life fitness and late-life mortality.

Systems genetics of influenza A virus-infected mice identifies TRIM21 as a critical regulator of pulmonary innate immune response.

Tripartite motif 21 (TRIM21) is a cytosolic Fc receptor that targets antibody-bound, internalized pathogens for destruction. Apart from this intrinsic defense role, TRIM21 is implicated in autoimmune diseases, inflammation, and autophagy. Whether TRIM21 participates in host interactions with influenza A virus (IAV), however, is unknown.

Traditional Chinese medicine as a novel therapy for colorectal cancer by modulating intestinal flora.

Colorectal cancer is a common clinical malignant tumor of the digestive tract, and intestinal flora has played an important role in the development of colorectal cancer. Bifidobacteria, as one of the main dominant florae in intestinal tract, can inhibit the occurrence and development of colorectal cancer through various mechanisms. Recent studies have shown that traditional Chinese medicine can regulate the abundance of bifidobacteria in intestinal tract and exhibit anti-tumor effects on colorectal cancer.

The Role of Thyroid Hormone Synthesis Gene-Related miRNAs Profiling in Structural and Functional Changes of The Thyroid Gland Induced by Excess Iodine.

At recent years, the impairment caused by iodine excess are paid more attention. However, there is still largely unknown about the exact mechanism induced by excessive iodine. MiRNAs have been found to act as biomarkers for a variety of diseases, whereas fewer studies focused on miRNAs related to a cluster of genes regulating thyroid hormone synthesis, such as NIS, Pendrin, TPO, MCT8, TSHR, TSHα, and TSHβ-related miRNAs in structural and functional changes of the thyroid gland induced by subchronic and chronic high iodine exposure.

The mechanism underlying fluoride-induced low-renin hypertension is related to an imbalance in the circulatory and local renin-angiotensin systems.

The renin-angiotensin system (RAS) is an important fluid regulation system in the body, and excessive activation of the circulatory or local RAS can increase blood pressure (BP). Excess fluoride can increase BP, although the underlying mechanism related to activation of the RAS remains unclear. Thus, the aim of this study was to elucidate the role of the RAS in fluoride-induced hypertension.

The Value of Circulating Tumor Cells and Tumor Markers Detection in Lung Cancer Diagnosis.

Objective: Circulating tumor cells are complete tumor cells with multi-scale analysis values that present a high potential for lung cancer diagnosis. To enhance the accuracy of lung cancer diagnosis, we detected circulating tumor cells by the innovated conical micro filter integrated microfluidic system.

Methods: We recruited 45 subjects of study, including 22 lung cancer patients, 2 precancerous patients, the control group including 14 healthy participants, and 7 patients with lung benign lesions in this prospective study.

Bring the life stages into the domain of basic and clinical pharmacology.

Completely distinct physiological conditions and immune responses exist among different human life stages. Age is not always consistent with the life stage. We proposed to incorporate the concept of the life stages into basic and clinical pharmacology, including clinical trials, drug labels, and drug usage in clinical practice.

A Historical Misconception in Clinical Trials of Drugs for Cancer-Age Grouping.

In clinical trials of cancer drugs, grouping by age is a very common grouping method, as it can allow for a visual comparison of the different pharmaceutical responses in patients at different age stages. Under the guidance of this thinking, many researchers use age grouping when studying clinical cancer drugs. However, even people at the same age may be at different stages in their lives, such as individuals who are going through puberty, menopause/andropause, or intermediate transition, as well as childhood and old age, affected by factors such as hormone levels, immune responses, ethnic groups, and regions.

Level of Estrogen in Females-The Different Impacts at Different Life Stages.

Historically, a high level of estrogen in women is regarded as the signature for a longer lifespan than men. Estrogen is known to be responsible for the development and regulation of the female reproductive system and secondary sex characteristics. Ovariectomy brings on numerous complications such as early menopause, heart disease, and osteoporosis.

An alternative approach-combination of lockdown and open in fighting COVID-19 pandemics.

As the COVID-19 pandemic enters its third year and the omicron variant becomes dominant, we propose an alternative strategy for dealing with COVID-19, called hybrid lockdown, that is, the combination of lockdown (the centralized and organized lockdown of the high-risk population) and free mobility (normal mobility) of the low-risk population. Such an approach will enable a country or region, especially with a high population density, to achieve significant prevention and control the effects of the COVID-19 pandemic at the least cost.

Mortality in Four Waves of COVID-19 Is Differently Associated with Healthcare Capacities Affected by Economic Disparities.

Background: The greatest challenges are imposed on the overall capacity of disease management when the cases reach the maximum in each wave of the pandemic.

Methods: The cases and deaths for the four waves of COVID-19 in 119 countries and regions (CRs) were collected. We compared the mortality across CRs where populations experience different economic and healthcare disparities.

Beta-caryophyllene prevents the defects in trabecular bone caused by Vitamin D deficiency through pathways instated by increased expression of klotho.

Aims: This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

Methods: A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.

Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model.

COVID-19 and chronic kidney disease (CKD) share similarity in sex bias and key genes in the disease pathway of sex difference. We investigated the sex difference of molecular pathways of four key players of these two diseases using an existing large set of whole genome expression profiles from the kidneys of female and male mouse models. Our data show that there is little to no correlation at the whole genome expression level between female and male mice among these four genes.