Exploration and Clinical Verification of the Blood Co-Expression Genes of Type 2 Diabetes Mellitus and Mild Cognitive Dysfunction in the Elderly.

With the development of society, the incidence of dementia and type 2 diabetes (T2DM) in the elderly has been increasing. Although the correlation between T2DM and mild cognitive impairment (MCI) has been confirmed in the previous literature, the interaction mechanism remains to be clarified. To explore the co-pathogenic genes in the blood of MCI and T2DM patients, clarify the correlation between T2DM and MCI, achieve the purpose of early disease prediction, and provide new ideas for the prevention and treatment of dementia. We downloaded T2DM and MCI microarray data from GEO databases and identified the differentially expressed genes associated with MCI and T2DM. We obtained co-expressed genes by intersecting differentially expressed genes. Then, we performed GO and KEGG enrichment analysis of co-DEGs. Next, we constructed the PPI network and found the hub genes in the network. By constructing the ROC curve of hub genes, the most valuable genes for diagnosis were obtained. Finally, the correlation between MCI and T2DM was clinically verified by means of a current situation investigation, and the hub gene was verified by qRT-PCR. A total of 214 co-DEGs were selected, 28 co-DEGs were up-regulated, and 90 co-DEGs were down-regulated. Functional enrichment analysis showed that co-DEGs were mainly enriched in metabolic diseases and some signaling pathways. The construction of the PPI network identified the hub genes in MCI and T2DM co-expression genes. We identified nine hub genes of co-DEGs, namely LNX2, BIRC6, ANKRD46, IRS1, TGFB1, APOA1, PSEN1, NPY, and ALDH2. Logistic regression analysis and person correlation analysis showed that T2DM was correlated with MCI, and T2DM increased the risk of cognitive impairment. The qRT-PCR results showed that the expressions of LNX2, BIRC6, ANKRD46, TGFB1, PSEN1, and ALDH2 were consistent with the results of bioinformatic analysis. This study screened the co-expressed genes of MCI and T2DM, which may provide new therapeutic targets for the diagnosis and treatment of diseases.

Shared peripheral blood biomarkers for Alzheimer's disease, major depressive disorder, and type 2 diabetes and cognitive risk factor analysis.

Background: Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM), and Major Depressive Disorder (MDD) have a higher incidence rate in modern society. Although increasing evidence supports close associations between the three, the mechanisms underlying their interrelationships remain elucidated. Objective: The primary purpose is to explore the shared pathogenesis and the potential peripheral blood biomarkers for AD, MDD, and T2DM. Methods: We downloaded the microarray data of AD, MDD, and T2DM from the Gene Expression Omnibus database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis to identify differentially expressed genes. We took the intersection of differentially expressed genes to obtain co-DEGs. Then, we performed GO and KEGG enrichment analysis on the common genes in the AD, MDD, and T2DM-related modules. Next, we utilized the STRING database to find the hub genes in the protein-protein interaction network. ROC curves were constructed for co-DEGs to obtain the most diagnostic valuable genes and to make drug predictions against the target genes. Finally, we conducted a present condition survey to verify the correlation between T2DM, MDD and AD. Results: Our findings indicated 127 diff co-DEGs, 19 upregulated co-DEGs, and 25 down-regulated co-DEGs. Functional enrichment analysis showed co-DEGs were mainly enriched in signaling pathways such as metabolic diseases and some neurodegeneration. Protein-protein interaction network construction identified hub genes in AD, MDD and T2DM shared genes. We identified seven hub genes of co-DEGs, namely, SMC4, CDC27, HNF1A, RHOD, CUX1, PDLIM5, and TTR. The current survey results suggest a correlation between T2DM, MDD and dementia. Moreover, logistic regression analysis showed that T2DM and depression increased the risk of dementia. Conclusion: Our work identified common pathogenesis of AD, T2DM, and MDD. These shared pathways might provide novel ideas for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosing and treating.

Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis.

Diabetes mellitus (DM) is known to be a risk factor for dementia, especially in the elderly population, and close associations between diabetes and Alzheimer disease (AD) have been determined. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists are insulin-sensitising drugs. In addition to their anti-diabetic properties, their effectiveness in preventing and decreasing cognitive impairment are the most recent characteristics that have been studied. For this study, we conducted a systematic review and meta-analysis to critically analyse and evaluate the existing data on the effects of PPAR-γ agonist therapy on the cognitive status of patients. For this purpose, we first analysed both early intervention and later treatment with PPAR-γ agonists, according to the disease status. The involved studies indicated that early PPAR-γ agonist intervention is beneficial for patients and that high-dose PPAR-γ therapy may have a better clinical effect, especially in reversing the effects of cognitive impairment. Furthermore, the efficacy of pioglitazone (PIO) seems to be promising, particularly for patients with comorbid diabetes. PIO presented a better clinical curative effect and safety, compared with rosiglitazone (RSG). Thus, PPAR-γ agonists play an important role in the inflammatory response of AD or DM patients, and clinical therapeutics should focus more on relevant metabolic indices.

Elevated serum uric acid is associated with cognitive improvement in older American adults: A large, population-based-analysis of the NHANES database.

Background: The many studies revealing a connection between serum uric acid (SUA) and dementia have reported conflicting results. This study sought to investigate the relations between SUA and cognitive function in older adults. Materials and methods: The sample was 2,767 American adults aged ≥60 years from the National Health and Nutrition Examination Survey 2011-2014. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's Disease test, animal fluency test, digit symbol substitution test, and composite z-score. Multivariate linear regression analyses were conducted to estimate the association between SUA and cognitive function. Results: SUA level and cognitive function were significantly, positively correlated. Age significantly correlated with the association between SUA and cognitive function. Conclusion: These findings support a connection between SUA and cognition, showing a positive link between SUA and cognitive scores among older American adults. We contend that a slight rise in uric acid within the normal range is advantageous for enhanced cognition. To confirm the precise dose-time-response relation, more tests will be needed.

Autologous Stem Cell Transplantation in Multiple Myeloma with Renal Failure: Friend or Foe?

Autologous stem cell transplantation (ASCT) is a standard treatment for multiple myeloma (MM), but the clinical response and renal curative effect in MM patients with renal failure (RF) remain controversial. The myeloma kidney disease has different types, and most are due to the direct toxic effects of light chain. Although ASCT can effectively clear the light chain, the data of renal function improvement are still limited. We reviewed the published literatures, focusing on the prospective studies, the retrospective analysis studies, and the case reports. RF patients who received ASCT displayed a low survival rate (OS: HR 1.95, 95% CI 1.020 to 3.720; I 2 = 64.9%, P = 0.014) and a shorter EFS/PFS (EFS/PFS: HR 1.53, 95% CI 1.090 to 2.140; I 2 = 0%, P = 0.669). However, ASCT was feasible and could have the similar clinical response outcomes compared with the normal renal function (CR: OR 1.013, 95% CI 0.569 to 1.804; I 2 = 48.5%, P = 0.101; PR: OR 1.013, 95% CI 0.342 to 1.226; I 2 = 46.3%, P = 0.144). Moreover, MM with RF after ASCT had a good improvement of renal function and melphalan is still an important factor affecting the treatment of ASCT.

Individual factors define the overall effects of dietary genistein exposure on breast cancer patients.

As an endocrine disruptor, tyrosine kinase inhibitor, and DNA methyltransferase inhibitor, genistein can interfere with breast cancer development. However, as the results of numerous studies are contradictory, it is unclear whether genistein plays a positive or negative role. Retrospective epidemiological studies have indicated that high genistein intake is related to reduced breast cancer risk, but this protective effect has not been reported in clinical trials. Additionally, rodent and cellular studies show that genistein promoted breast cancer progression. Obviously, genistein's bioactivities do not solely depend upon the dose, and simply discussing the overall effects of genistein without considering individual factors is unrealistic. The purpose of this review was to collect relevant studies (over 164) on genistein and breast cancer that were published on PubMed from 1984 to 2019 and to summarize the impact of key individual factors on the bioactivities of genistein in breast cancer prevention and treatment. Furthermore, the related potential molecular mechanisms were explored to explain the contradictions in genistein-breast cancer studies. Our results showed that the intake mode and metabolic characteristics of genistein, as well as the menopausal status, estrogen receptor expression pattern, and gene mutations of the patient, are important factors that should be included when discussing the bioactivities of genistein. A better understanding of the influence of individual factors may enable the precise prediction of personalized responses to dietary genistein exposure. Given that the current information on genistein is mostly restricted to the cellular level, more comprehensive human studies should be performed to clarify the relationship between genistein and breast cancer.

Spotlights on Antibiotic-induced Acute Kidney Injury: the Evidence to Date.

Acute kidney injury (AKI) is a frequent and wide complication of antibiotics therapy. In the present review article, we assessed the epidemiology, pathogenesis, risk factors, and clinical manifestation of antibiotic-induced AKI. The risk factors for the occurrence of antibiotic-induced AKI include medical comorbidities, coexisting drug therapies and the dosage, and therapeutic period of antibiotics. The prognosis of antibiotic-induced AKI varies by antibiotics types. This review summarizes the clinical controversy of antibiotic treatment and the future clinical recommendations.

ERß modulates genistein's cisplatin-enhancing activities in breast cancer MDA-MB-231 cells via P53-independent pathway.

As one of the typical food-derived phytoestrogens, genistein (GEN) could bind to estrogen receptor (ER) and was reported to be closely related to breast cancer. Our former research showed that GEN interfered with the anti-tumor effects of cisplatin (CIS) in breast cancer MCF-7 (ERα+/ERß-) cells. However, it is not clear whether ER expression pattern affects GEN's modulation on CIS's activity. In the present study, breast cancer ERß knockdown (ERßKD) MDA-MB-231 (ERα-/ERß+) cell model was established via ERß RNAi lentivirus infection. The role of ERß expression in GEN's bioeffects on cells' response to CIS was investigated and was further double-checked by pathway-specific inhibitor PHTPP. Consistent results were harvested through cell viability analysis, cell cycle distribution flow cytometry, TUNEL staining, and expression detection of key biomarkers, Bax, Bcl-2, P21, P53, and cleaved caspase-3. Compared with the control group, PHTPP-treated or ERßKD cells exhibited higher sensitivity to both GEN and CIS treatment. GEN and CIS showed synergistic effects only in ERß-deficient cells. This effect mainly resulted in G2 phase arresting and apoptosis induction with the upregulation of P21 and Bax/Bcl-2 protein level. Besides, P53 expression was strikingly suppressed in ERß-deficient cells. This indicated ERß pathway deficiency might enhance GEN-CIS bioactivity via the downregulation of P53. In summary, our data imply that daily intake of GEN-rich diet could collaborate with CIS anti-tumor treatment in ERα-/ERß- breast cancer cases. ERß pathway might be one of the potential targets which elicit GEN's positive effects in ERα- breast cancer patients.

A Pilot Study on the Psychosocial Health and Living Quality of Left-Behind Children in a Remote City of China.

Purpose: With the rapid economic development, China has undergone a large-scale migration, with many children left behind due to parental migration for better income. Little is known about the psychosocial health and living quality of the Chinese left-behind children (LBC) in remote cities, so this study aims at investigating the emotional and behavioral problems as well as the living qualities of LBC in remote cities of China. Methods: In this pilot cross-sectional study, 45 schoolchildren (10-12 years old) from Guiyang, a remote city in China, were enrolled in the sampling. The Strength and Difficulties Questionnaire (SDQ) and Quality of Life Scale for Children and Adolescents (QLSCA) were used to evaluate the psychosocial health and living quality. The differences between LBC and control children and correlation factors were analyzed in this study. Results: LBC had a statistically significantly higher score in SDQ than in the control group with p-values that were all <0.01. The prosocial score in LBC was significantly lower than that of the control children (p<0.01). The scores on QLSCA were significantly lower for the LBC than for their counterparts (p<0.01). The emotional and behavioral problems (SDQ scores) and the living quality (QLSCA scores) are highly correlated. Conclusion: This preliminary study identified the severity of the psychosocial problem and the lower living quality with LBC in the remote city of China. This problem may relate to the lower education level of their caregivers. The LBC in remote cities of China need more psychosocial and educational support from schools and communities.