Effects of Varied Sulfamethazine Dosage and Exposure Durations on Offspring Mice.

The development of antibiotics was a turning point in the history of medicine; however, their misuse and overuse have contributed to the current global epidemic of antibiotic resistance. According to epidemiological studies, early antibiotic exposure increases the risk of immunological and metabolic disorders. This study investigated the effects of exposure to different doses of sulfamethazine (SMZ) on offspring mice and compared the effects of exposure to SMZ on offspring mice in prenatal and early postnatal periods and continuous periods. Furthermore, the effects of SMZ exposure on the gut microbiota of offspring mice were analyzed using metagenome. According to the results, continuous exposure to high-dose SMZ caused weight gain in mice. IL-6, IL-17A, and IL-10 levels in the female offspring significantly increased after high-dose SMZ exposure. In addition, there was a significant gender difference in the impact of SMZ exposure on the gut microbiota of offspring: Continuous high-dose SMZ exposure significantly decreased the relative abundance of Ligilactobacillus murinus, Limosilactobacillus reuteri, Lactobacillus johnsonii, and Bifidobacterium pseudolongum (p < 0.05) in female offspring mice; however, these significant changes were not observed in male offspring mice.

A gut aging clock using microbiome multi-view profiles is associated with health and frail risk.

Age-related changes in the microbiome have been reported in previous studies; however, direct evidence for their association with frailty is lacking. Here, we introduce biological age based on gut microbiota (gAge), an integrated prediction model that integrates gut microbiota data from different perspectives with potential background factors for aging assessment. Simulation results show that, compared with a single model, the ensemble model can not only significantly improve the prediction accuracy, but also make full use of the data in unpaired samples. From this, we identified markers associated with age development and grouped markers into accelerated aging and mitigated aging according to their effect on the prediction. Importantly, the application of gAge to an elderly cohort with different frailty levels confirmed that gAge and its predictive residuals are closely related to the individual's health status and frailty stage, and age-related markers overlap significantly with disease and frailty characteristics. Furthermore, we applied the gAge prediction model to another independent cohort of the elderly population for aging assessment and found that gAge could effectively represent the aging population. Overall, our study explains the association between the gut microbiota and frailty, providing potential targets for the development of gut microbiota-based targeted intervention strategies for aging.

Role of comprehensive geriatric assessment in screening for mild cognitive disorders.

BACKGROUND: The role of comprehensive geriatric assessment (CGA) in screening for mild cognitive disorders was not known. AIM: To evaluate the role of CGA in screening for mild cognitive disorders. METHODS: A total of 100 elderly people who underwent health examinations in our hospital and community between January 2020 and December 2021 were included for analysis. Using Petersen as the diagnostic gold standard, healthy individuals were included in the control group and patients with mild cognitive impairment were assigned to the study group. The correlation between the cognitive function of the patients and their baseline clinical profiles was analyzed. Patients' Montreal Cognitive Assessment (MoCA) and CGA screening results were compared, and the sensitivity and specificity were calculated to assess the screening role of CGA. RESULTS: CGA assessment yielded higher diagnostic accuracy than MoCA. The results of the multivariate regression analysis showed no correlation of gender, age, body mass index and literacy with cognitive function. Patients with mild cognitive impairment obtained significantly lower MoCA scores than healthy individuals (P < 0.05). In the CGA scale, patients with mild cognitive impairment showed significantly lower Mini-mental State Examination, Miniature Nutritional Assessment and Berg Balance Scale scores, and higher Activity of Daily Living, Instrumental Activities of Daily Living Scale and Frailty Screening Inventory scores than healthy individuals (P < 0.05), whereas the other assessment scales showed no significant differences (P > 0.05). The CGA provides higher diagnostic sensitivity and specificity than the MoCA (P < 0.05). CONCLUSION: CGA allows accurate identification of mild cognitive impairment with high sensitivity and specificity, facilitating timely and effective intervention, and is thus recommended for clinical use.

Prevalence and possible factors of cognitive frailty in the elderly with hypertension and diabetes.

Background: Cognitive frailty is the coexistence of physical frailty and mild cognitive impairment. Research shows that cognitive frailty is related to an increased risk of hospitalization, mortality, disability, and dementia. Diabetes and hypertension are common risk factors for physical frailty and cognitive impairment. However, the factors influencing cognitive frailty in the elderly with hypertension and diabetes are still unclear. This study aimed to investigate the possible factors influencing cognitive frailty in the elderly with hypertension and diabetes. Methods: A cross-sectional study was conducted. We evaluated people over 60 years with hypertension and diabetes who underwent physical examination in Wuxi Xin'an Community Health Service Center. Frail scale, Montreal Cognitive Assessment-Basic and clinical dementia rating were used to assess cognitive frailty. We collected demographic characteristics, hypertension and diabetes-related laboratory indicators of the participants. We also used various scales to assess the overall health status of the elderly. Results: Approximately 20.8% of the participants were determined to have cognitive frailty in elderly adults with hypertension and diabetes. These participants were older, had a lower monthly income, and included a higher proportion of peasants. They also had a higher level of depression (p = 0.037), higher risk of falls (p = 0.000), higher risk of malnutrition (p = 0.002), poorer ability to perform activities of daily living (ADL) (p = 0.000), and less social support (p = 0.030). Multivariate regression analysis was used to further assess the factors for cognitive frailty. After adjusting for possible confounders, age and ADL score emerged as risk factors, whereas high monthly income decreased the risk of cognitive frailty. Conclusion: Cognitive frailty is correlated with age, income, and ability to perform daily living activities in the elderly with diabetes and hypertension. Closer attention to the elderly who have low income and poor self-care ability may play an important role in the early prevention of cognitive frailty and even dementia.

Inhibition of Heat Shock Protein 90 Attenuates the Damage of Blood-Brain Barrier Integrity in Traumatic Brain Injury Mouse Model.

Heat shock protein 90 (HSP90) is widely found in brain tissue. HSP90 inhibition has been proven to have neuroprotective effects on ischemic strokes. In order to study the role of HSP90 in traumatic brain injury (TBI), we carried out the present study. A novel inhibitor of the HSP90 protein, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DA), has been investigated for its function on the blood-brain barrier (BBB) damage after traumatic brain injury (TBI) in mouse models. These C57BL/6 mice were used as a TBI model and received 17-DA (0.1 mg/kg/d, intraperitoneally) until the experiment ended. To find out whether 17-DA may protect against TBI in vitro, bEnd.3 cells belonging to mouse brain microvascular endothelium were used. The HSP90 protein expressions were raised after TBI at the pericontusional area, especially at 3 d. Our study suggested that 17-DA-treated mice improved the recovery ability of neurological deficits and decreased brain edema, Evans blue extravasation, and the loss of tight junction proteins (TJPs) post-TBI. 17-DA significantly promoted cell proliferation and alleviated apoptosis by inhibiting the generation of intracellular reactive oxygen species (ROS) to downregulate cleaved caspase-3, matrix metallopeptidase- (MMP-) 2, MMP-9, and P-P65 in bEnd.3 cells after the injury. As a result, we assumed that the HSP90 protein was activated post-TBI, and inhibition of HSP90 protein reduced the disruption of BBB and improved the neurobehavioral scores in a mouse model of TBI through the action of 17-DA, which inhibited ROS generation and regulated MMP-2, MMP-9, NF-κB, and caspase-associated pathways. Thus, blocking HSP90 protein may be a potential therapeutic strategy for TBI.

Gut Microbiota and Targeted Biomarkers Analysis in Patients With Cognitive Impairment.

Gut microbial alteration is closely associated with brain disorders including cognitive impairment (CI). Gut microbes have the potential to predicate the development of diseases. However, the gut microbial markers for CI remain to be elucidated. In this study, the gut microbial alterations were assessed using16S rRNA sequencing, and identified the gut microbial markers using a random forest model. The results showed that there were significant gut microbial differences between the control and CI groups based on beta diversity (p < 0.002). Patients with CI had higher abundances of Actinobacteria and Proteobacteria but lower proportions of Bcateroidetes and Firmicutes vs. that in the control group. Patients had 39 special genera and the control subjects had 11 special genera. Furthermore, 11 genera such as Blautia, Roseburia, and Lactococcus and 18 genera such as Lactobacillus, Ruminococcus 2, and Akkermansia were the differential taxa in the control and CI groups, respectively. Gene functions related to nutrient metabolisms were upregulated in patients with CI. This suggested that the huge differences in gut microbes between the two groups and gut microbiota had the potential to predicate the development of CI. Based on machine learning results, 15 genera such as Lactobacillus, Bifidobacterium, and Akkermansia were selected as the optimal marker set to predicate CI with an area under curve (AUC) value of 78.4%. The results revealed the gut microbial markers for CI and provided a potential diagnosis tool to prevent the development of CI in the elderly.

A recommended amount of hydrolyzed protein improves physiological function by regulating gut microbiota in aged mice.

Dietary proteins play a critical role in maintaining the health of elderly people. Although experts recommend that elderly people consume more protein, a high-protein diet may add to the burden of elderly people with degraded digestion and absorption functions. The effects of a normal or high-protein diet and those of a whole or hydrolyzed protein diet on bone and muscle health and gastrointestinal function were evaluated in aged female C57BL/6J mice. The hydrolyzed protein diet with 14.7% protein energy ratio (HNP) contributed to the maintenance of weight and an increase in bone and muscle mass. Further, the overall aging situation was improved by the consumption of this diet. However, the hydrolyzed protein diet with 21.3% protein energy ratio (HHP) increased the levels of LPS, IL-6, IL-10, and TNF-α in serum. Additionally, the small intestine structure was damaged, and the goblet cell number was decreased in the HHP and whole protein with 21.3% protein energy ratio (HP) groups. The relative abundances of Streptococcus and Peptococcus were decreased while that of Bifidobacterium was increased in HNP group compared with the whole protein with 14.7% protein energy ratio (NP) and HP groups. Undigested proteins entering the intestine may cause undesirable changes in gut microbiota, which adversely affect the aging body in NP and HP groups. In summary, hydrolyzed proteins are more advisable than untreated dietary protein in aged mice. This study aimed to provide guidance for daily diet for elderly people, and provide additional information to industry in order to guide their future food development.

Predictive Value of Gut Microbiome for Cognitive Impairment in Patients with Hypertension.

A connection exists between hypertension (HTN) and cognitive impairment (CI) or gut microbiota (GM) and neuropsychiatric disease. However, the link between GM and HTNCI has not been illustrated. This study endeavoured to profile the landscape of GM in HTNCI patients and evaluate the value of GM as HTNCI biomarkers. We recruited 128 patients with hypertension and assigned them to two groups of different MoCA scores. Clinical and biological data were recorded. GM composition was illustrated with 16S ribosomal RNA sequencing, and the dominant species were identified by linear discriminant analysis Effect Size (LEfSe). It showed higher abundance of TM7 and lower abundances of Veillonella and Peptoniphilus in the HTNCI group than in the HTN without cognitive impairment (HTNnCI) group. We next clarified the link between GM and MoCA scores or HTNCI factors. KEGG analysis revealed the involvement of decreased bile secretion. An evident correlation showed up between HTNCI and Veillonella abundance (P = 0.0340). We concluded that some representative GM species, especially Veillonella, could predict cognitive impairment in hypertension patients, making them potential benchmarks of HTNCI.

Pyroptosis in the Initiation and Progression of Atherosclerosis.

Pyroptosis, a newly discovered form of programmed cell death, is characterized by cell swelling, the protrusion of large bubbles from the plasma membrane and cell lysis. This death pathway is mediated by the pore formation of gasdermin D (GSDMD), which is activated by human caspase-1/caspase-4/caspase-5 (or mouse caspase-1/caspase11), and followed with the releasing of both cell contents and proinflammatory cytokines. Pyroptosis was initially found to function as an innate immune effector mechanism to facilitate host defense against pathogenic microorganisms, and subsequent studies revealed that pyroptosis also plays an eventful role in inflammatory immune diseases and tumor resistance. Recent studies have also shown that pyroptosis is involved in the initiation, the progression and complications of atherosclerosis. Here, we provide an overview of the role of pyroptosis in atherosclerosis by focusing on three important participating cells: ECs, macrophages, and SMCs. In addition, we also summarized drugs and stimuli that regulate the progression of atherosclerosis by influencing cell pyroptosis.

lncRNA LINC00460 Functions as a Competing Endogenous RNA and Regulates Expression of BGN by Sponging miR-149-5p in Colorectal Cancer.

BACKGROUND AND AIM: There are an increasing number of studies indicating the important roles served by long non-coding RNAs (lncRNAs) in the development of different types of cancer. LINC00460 is a novel identified lncRNA that was found to be upregulated in colorectal cancer. However, the biological roles of LINC00460 in colorectal cancer have yet to be fully elucidated. This study was aimed to investigate the functions and molecular mechanisms of LINC00460 on colorectal cancer metastasis. METHODS: Expression of LINC00460 and biglycan (BGN) in colorectal cancer tissues and cell lines were quantified by real time PCR or western blotting assay. Cell migration and invasion assays were performed to determine the effect of LINC00460 on tumor metastasis in vitro. The binding interaction between microRNA-149-5p and LINC00460 was revealed by luciferase reporter assay. RESULTS: In the present study, lncRNA LINC00460 was shown to be upregulated in colorectal cancer tissues, and overexpression of LINC00460 significantly promoted metastasis of colorectal cancer in vitro. Furthermore, miR-149-5p interacted with LINC00460, and they negatively regulated expression of each other. Transfection of miR-149-5p mimics partially counteracted the tumor metastasis-promoting effects induced by LINC00460 overexpression. Finally, overexpression of LINC00460 upregulated the expression levels of biglycan, a target gene of miR-149-5p, which has also been identified as an oncogenic driver in colorectal cancer. CONCLUSION: Taken together, the present study demonstrated that LINC00460 promoted metastasis of CRC by sponging miR-149-5p and thereby affecting biglycan expression levels.

The diversity of gut microbiota in type 2 diabetes with or without cognitive impairment.

BACKGROUND: Diabetes is associated with a high risk of developing cognitive impairment, but the underlying mechanism remains unclear. Recent studies have found that gut microbiota may be involved in the progression of diabetes-associated cognitive impairment. AIMS: To analyze the diversity of gut microbiota in type 2 diabetes with or without cognitive impairment METHODS: 16S rRNA sequencing was used to detect the gut microbiota composition in 154 type 2 diabetes (T2DM) subjects RESULTS: Among 154 elderly T2DM participants included in our study, 73 with normal and 81 with impaired cognition. Lower levels of hemoglobin and HDL were observed in subjects with cognitive impairment. Patients with cognitive impairment had a lower abundance of Tenericutes. Comparison at the genus level revealed that T2DM patients with cognitive impairment had a decreased abundance of Bifidobacterium and unranked-RF39 and an increased abundance of Peptococcus and unranked-Leuconostocaceae. Additionally, the relative abundance of Veillonella and Pediococcus were decreased in subjects with cognitive impairment. Furthermore, the relative abundance of 7 sub-functions was significantly changed in the group with cognitive impairment. Calcium signaling pathways and the Renin-angiotensin system were upregulated in the cognitive impairment group while GnRH signaling, Fc gamma R-mediated phagocytosis, endocytosis, isoflavonoid biosynthesis, and cytochrome P450 were deregulated. CONCLUSION: Bifidobacterium may be associated with cognition in T2DM. Calcium signaling and renin-angiotensin system were shown to be associated with diabetes-associated cognitive impairment through gut microbiota.