Correlation Between Resilience and Social Support in Elderly Ischemic Stroke Patients.

OBJECTIVE: Social support can be divided into emotional support, tool support, and information support in function or mode. Emotional support is an encouragement, expressed as love and care, respect and value, encouragement and compassion, and psychological resilience due to adaptation to adversity and stressors, which is conducive to personal positive psychological adjustment and good functional status. This study aims to explore the status of resilience and social support in elderly stroke patients and examine the correlation between the 2 factors. METHODS: Convenience sampling was used to survey 280 elderly stroke ischemic patients admitted to the Department of Neurology in our hospital from January to December 2020. General information, resilience, and social support were assessed through questionnaires. RESULTS: The participants had a moderate level of resilience, with an average score of 63.77 ± 9.99. The total social support score ranged with an average score of 33.72 ± 5.77, indicating a relatively low level of social support. After the Pearson correlation analysis, there was a positive correlation between resilience and social support, namely, r = 0.277, P < 0.05. CONCLUSIONS: Enhancing social support among elderly stroke patients is an effective way to improve their psychological resilience.

Identification of hub genes in bladder transitional cell carcinoma through ceRNA network construction integrated with gene network analysis.

Bladder transitional cell carcinoma (BTCC) forms more than 90% of bladder cancer cases. It brings challenges to the early diagnosis and therapy of BTCC, due to lack of efficient screening biomarkers. We used weighted gene co-expression network analysis (WGCNA) combined competing endogenous RNA (ceRNA) network construction depending on TCGA datasets to investigate potential hub genes and regulatory pathways associated with occurrence and progression of BTCC. We further used real-time polymerase chain reaction (RT-PCR) to validate the relative expression genes correlated with BTCC. By WGCNA, the gene co-expression module with 11 genes was found corelated with BTCC tumour stage and prognosis after survival analyses. Ultimately, we put 100 highly stage-related genes into the above constructed ceRNA network and then constructed another new network. Among them, all elements in AC112721.1/LINC00473/AC128709.1-hsa-mir-195-RECK and LINC00460-hsa-mir-429-ZFPM2 axes were simultaneously corelated with overall survival. RT-PCR showed that AKAP12 was downregulated in tumour tissues. The hub genes screened out in the present study may provide ideals for further treatment on BTCC.

Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.

Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.

[Effect of LINC00174 on the Malignant Proliferation of Multiple Myeloma Cells and Its Related Mechanism].

OBJECTIVE: To explore the biological function of LINC00174 in multiple myeloma (MM). METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of LINC00174 and miR-150 in peripheral blood of MM patients and MM cell lines. EdU staining and flow cytometry were used to detect the effects of LINC00174 and miR-150 on the proliferation and apoptosis of MM cells. Western blot was used to detect the expressions of proliferation marker nuclear-related antigen Ki67, apoptosis-related protein cleaved caspase-3 and transcription factor forkhead box protein P1 (FOXP1). Bioinformatics and dual-luciferase reporter assay were used to verify the targeting relationship between LINC00174 and miR-150 and the targeting relationship between miR-150 and FOXP1. RESULTS: The level of LINC00174 was significantly increased in peripheral blood of MM patients and MM cell lines (P <0.05). Compared with NC-siRNA group, the expression of LINC00174 was significantly reduced in LINC00174-siRNA group, the proliferation of U266 cells was reduced, the apoptosis rate was significantly increased, the level of Ki67 protein was reduced, and the level of cleaved caspase-3 protein was increased (all P <0.05). LINC00174 targeted regulation of the expression of miR-150. Compared with LINC00174-siRNA+NC inhibitor group, the expression of miR-150 in U266 cells in LINC00174-siRNA+miR-150 inhibitor group was significantly reduced, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05). FOXP1 is the target gene of miR-150. Compared with NC mimic group, the expression of FOXP1 protein in miR-150 mimic group was significantly reduced, the cell proliferation was reduced, the apoptosis rate was significantly increased, Ki67 protein level was decreased, and the level of cleaved caspase-3 was increased. Compared with miR-150 mimic + vector group, the expression of FOXP1 protein in miR-150 mimic + pcDNA-FOXP1 group was significantly increased, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05). CONCLUSION: LINC00174 promotes the proliferation of MM cells and inhibits cell apoptosis by regulating the miR-150/ FOXP1 axis.

Recent Advances in Therapeutic Modalities Against Breast Cancer-Related Lymphedema: Future Epigenetic Landscape.

Background: Lymphedema is a significant postsurgical complication observed in the majority of breast cancer patients. These multifactorial etiopathogenesis have a significant role in the development of novel diagnostic/prognostic biomarkers and the development of novel therapies. This review aims to ascertain the epigenetic alterations that lead to breast cancer-related lymphedema (BCRL), multiple pathobiological events, and the underlying genetic predisposing factors, signaling cascades pertinent to the lapses in effective prognosis/diagnosis, and finally to develop a suitable therapeutic regimen. Methods and Results: We have performed a literature search in public databases such as PubMed, Medline, Google Scholar, National Library of Medicine and screened several published reports. Search words such as epigenetics to induce BCRL, prognosis/diagnosis, primary lymphedema, secondary lymphedema, genetic predisposing factors for BRCL, conventional therapies, and surgery were used in these databases. This review described several epigenetic-based predisposing factors and the pathophysiological consequences of BCRL, which affect the overall quality of life, and the interplay of these events could foster the progression of lymphedema in breast cancer survivors. Prognosis/diagnostic and therapy lapses for treating BCRL are highly challenging due to genetic and anatomical variations, alteration in the lymphatic vessel contractions, and variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors. Conclusion: We compared the efficacy of various conventional therapies for treating BCRL as a multidisciplinary approach. Further substantial research is required to decipher underlying signaling epigenetic pathways to develop chromatin-modifying therapies pertinent to the multiple etiopathogenesis to explore the correlation between the disease pathophysiology and novel therapeutic modalities to treat BCRL.

The Effect of the Comprehensive Reform of Agricultural Water Prices on Farmers' Planting Structure in the Oasis-Desert Transition Zone-A Case Study of the Heihe River Basin.

The comprehensive reform of agricultural water prices is an important policy for promoting the high-quality sustainable development of agriculture and ensuring national water security. In this study, based on farmer survey data from different water price policy implementation areas in the oasis-desert transition zone of the Heihe River Basin (HRB), crops are divided into high-water-consuming crops and low-water-consuming crops based on the average water consumption per hm2. The content of this study consists of two main parts: first, the study explores the response of farmers to different agricultural water price policies by comparing the impact of uniform water price and tiered water price policies on their planting structure. Second, it studies the areas where the tiered water price policy is implemented to verify the impact of price signals on farmers' production decisions. The results show that, compared with the uniform water price policy, the implementation of the tiered water price policy will significantly reduce the proportion of high-water-consuming crops planted when other conditions remain unchanged. Under the tiered water price policy, the increase in water prices will reduce the proportion of farmers planting high-water-consuming crops, but the difference is not significant. This result reveals that when the opportunity cost of irrigation water increases, farmers will increase the proportion of low-water-consuming crops. The findings also indicate that a higher educational level, improved land inflow, the number of crop types, and satisfaction with the current subsidy policy will help increase the proportion of low-water-consuming crops. However, an increase in the family-cultivated land area will reduce the area of low-water-consuming crops.

SARS-CoV-2: An Updated Review Highlighting Its Evolution and Treatments.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

Posterior reversible encephalopathy in a pregnant woman without preeclampsia or eclampsia: A case report.

BACKGROUND: We report a case of a pregnant woman who presented posterior reversible encephalopathy syndrome (PRES) without pre-eclampsia, eclampsia, or any other common causes of PRES. METHODS: A 32-year-old primigravida at 25 weeks and 4 days of gestation was admitted to neurology department because of suffering intermittent headache, hearing loss, memory loss with mental and behavioral disorder, and blurred vision for 1 month. She was healthy before without hypertension, migraine, or other medical or family history. Brain magnetic resonance imaging (MRI) revealed diffuse symmetrical high-signal intensity lesions in the white matter, medulla oblongata, without enhancement. After completely multidisciplinary discussion and with the family of the patient, she accepted termination of pregnancy. RESULTS: After the operation, the patient improved symptomatically. The follow-up MRI showed a decrease of the white matter lesion after 3 months and complete recovery at postoperative 6 months. The patient returned to work without any neurological sequelae. CONCLUSION: It might widen the cause spectrum of PRES that pregnancy itself without pre-eclampsia, eclampsia, or any other known risk factors could cause PRES. Pregnancy with acute or subacute leukoencephalopathy should be screened related causes and risk factors carefully. Hormonal fluctuations during the pregnancy might account for pregnancy-related PRES.

Differentiation of Parkinson's disease and Parkinsonism predominant multiple system atrophy in early stage by morphometrics in susceptibility weighted imaging.

Background and purpose: We previously established a radiological protocol to discriminate multiple system atrophy-parkinsonian subtype (MSA-P) from Parkinson's disease (PD). However, we do not know if it can differentiate early stage disease. This study aimed to investigate whether the morphological and intensity changes in susceptibility weighted imaging (SWI) of the lentiform nucleus (LN) could discriminate MSA-P from PD at early stages. Methods: We retrospectively enrolled patients with MSA-P, PD and sex- and age-matched controls whose brain MRI included SWI, between January 2015 and July 2020 at the Movement Disorder Center. Two specialists at the center reviewed the medical records and made the final diagnosis, and two experienced neuroradiologists performed MRI analysis, based on a defined and revised protocol for conducting morphological measurements of the LN and signal intensity. Results: Nineteen patients with MSA-P and 19 patients with PD, with less than 2 years of disease duration, and 19 control individuals were enrolled in this study. We found that patients with MSA- P presented significantly decreased size in the short line (SL) and corrected short line (cSL), ratio of the SL to the long line (SLLr) and corrected SLLr (cSLLr) of the LN, increased standard deviation of signal intensity (SIsd_LN, cSIsd_LN) compared to patients with PD and controls (P < 0.05). With receiver operating characteristic (ROC) analysis, this finding had a sensitivity of 89.5% and a specificity of 73.7% to distinguish MSA- P from PD. Conclusion: Compared to PD and controls, patients with MSA-P are characterized by a narrowing morphology of the posterior region of the LN. Quantitative morphological changes provide a reference for clinical auxiliary diagnosis.

Higher BMI and lower femoral neck strength in males with type 2 diabetes mellitus and normal bone mineral density.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and osteoporosis are two age-associated diseases. Body mass index (BMI) is positively associated with osteoporosis or osteopenia in T2DM population. Bone mineral density does not necessarily reflect the alterations in bone microarchitecture. Our aims were to investigate the relationship between BMI and femoral neck strength in males with T2DM and normal range of bone mineral density (BMD). METHODS: This study enrolled 115 males (median age 53.3 years) with T2DM and normal BMD. Femoral neck strength indexes, including compression strength index (CSI), bending strength index (BSI), impact strength index (ISI), were calculated by parameters generated from Dual-energy X-ray absorptiometry software. Pearson correlation analysis was performed to evaluate the relationships between BMI and femoral neck strength variables. RESULTS: Compared with T2DM-normal weight group, T2DM-overweight group and T2DM-obesity group had a higher femur neck and total femur BMDs. Cross sectional moment of inertia (CSMI), cross sectional area (CSA), section modulus (SM) were significantly higher (all p<0.05), and buckling ratio (BR) (6.35±2.08 vs 7.18±1.71) was lower in T2DM-obesity group than in T2DM-normal weight group. Compared with T2DM-normal weight group, CSI (all p<0.001), BSI (all p<0.001), ISI (all p<0.001) were significantly reduced in T2DM-obesity and T2DM-overweight groups. Pearson correlation analysis indicated that BMI was negatively correlated with CSI (r= - 0.457, p<0.001), BSI(r = -0.397, p<0.001), ISI (r = - 0.414, p<0.001). CONCLUSIONS: Higher BMI is associated with lower femoral neck strength in males with T2DM and normal BMD. It implies that femoral neck fracture risk increases in obese and diabetic males, despite their high bone density.

Criteria for Treatment Response in Myasthenia Gravis: Comparison Between Absolute Change and Improvement Percentage in Severity Scores.

Background: The absolute change in the severity score between the baseline and pre-specified time frame (absolute criterion) was recommended as a criterion for myasthenia gravis (MG) treatment response. But heterogeneity of disease severity might dilute major changes in individual patients. The rationality of relative criterion (improvement percentage) had not been evaluated in treatment response in patients with MG. Objectives: To investigate the consistency between an absolute criterion and a relative criterion in the evaluation of treatment response in patients with MG. Methods: We retrospectively analyzed the treatment response to a 3-month standardized treatment protocol with only glucocorticoid in 257 MG patients native to immunological treatments. With the commonly used absolute criterion, cut-offs of relative criteria were generated with the receiver operating characteristic (ROC) curve in the whole cohort and in patients with different degrees of baseline severity stratified by pre-treatment quantitative myasthenia gravis score (QMGS). The consistency between absolute and relative criteria was examined with Cohen's Kappa test and Venn diagrams. Results: The absolute and relative criteria had an overall substantial consistency (Kappa value, 0.639, p < 0.001) in the cohort. The Kappa values were substantial to almost perfect in mild and moderate groups and moderate in severe groups between the absolute and relative criteria (all p ≤ 0.001). More patients were classified as responsive with an absolute criterion while as unresponsive with a relative criterion in the moderate and severe groups. Conclusions: The overall consistency between absolute and relative criteria was substantial in the whole cohort. The inconsistency between the two criteria was mainly from the moderate or severe patients at the baseline.

Clinicopathologic Profiles of Sporadic Late-Onset Nemaline Myopathy: Practical Importance of Anti-α-Actinin Immunostaining.

BACKGROUND AND OBJECTIVES: Sporadic late-onset nemaline myopathy (SLONM) is a treatable or otherwise fatal myopathy. Diagnosis of SLONM is still challenging, and no therapeutic consensus has been achieved. Here, we reported the clinicopathologic features and long-term follow-up data of SLONM in a Chinese cohort. METHODS: We performed a retrospective evaluation of clinical, pathologic, and treatment outcomes of 17 patients with SLONM diagnosed between March 1986 and April 2021 at our neuromuscular center. Immunohistochemistry (IHC) with antibodies against 5 Z-disc-associated proteins was performed in the muscle biopsies of SLONM to identify a potential pathologic marker in aid of diagnosis. In comparison, we also performed muscle IHC in patients with selective type II fiber atrophy (n = 22), neurogenic atrophy (n = 22), mitochondrial myopathy (n = 5), immune-mediated necrotizing myopathy (n = 5), and normal controls (n = 5). RESULTS: Most of the patients exhibited asymmetric limb muscles weakness (71%, 12/17) and neck extensor weakness (53%, 9/17). Immunofixation electrophoresis was performed in 11 patients, and 4 of them were identified with monoclonal gammopathy of undetermined significance (MGUS). EMG from 16 patients demonstrated a myopathic pattern with spontaneous activities in 69% (11/16) of them. Muscle MRI showed preferential involvement of paraspinal, gluteus minimus and medius, semimembranosus, and soleus muscles. Suspected nemaline bodies on modified Gomori trichrome were confirmed by IHC using anti-α-actinin antibody (100%, 17/17), anti-myotilin antibody (94%, 16/17), anti-desmin antibody (94%, 16/17), anti-α-B crystallin antibody (65%, 11/17), and anti-telethonin antibody (18%, 3/17) with various positive rates. Notably, anti-α-actinin IHC showed the highest percentage of strongly positive staining (77%, 13/17), being the only one without negative results. Moderate improvement following autologous stem cell transplantation (ASCT) was noted in 3/4 patients with MGUS; favorable outcomes were also achieved in 6/7 patients without MGUS, including 3 patients with complete recovery who were given a combined treatment of prednisone and another immunosuppressant. DISCUSSION: SLONM is a treatable myopathy with ASCT or traditional immunotherapy, especially when combined with steroids and immunosuppressants. Anti-α-actinin immunostaining is the most reliable pathologic marker to identify rod-bearing fibers, and it should be performed routinely in adult patients with undiagnosed nonnecrotic myopathies.

A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection.

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for γδ IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the γδ IEL compartment under homeostatic conditions has yet to be determined. We identified a novel γδ IEL hyperproliferative phenotype that arises early in life and is characterized by expansion of multiple Vγ subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal γδ IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in γδ IELs. Further, we identified two guilds of small intestinal or fecal bacteria represented by 12 amplicon sequence variants (ASV) that are strongly associated with γδ IEL expansion. Using intravital microscopy, we find that hyperproliferative γδ IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate γδ IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier.

Modulation of MagR magnetic properties via iron-sulfur cluster binding.

Iron-sulfur clusters are essential cofactors found in all kingdoms of life and play essential roles in fundamental processes, including but not limited to respiration, photosynthesis, and nitrogen fixation. The chemistry of iron-sulfur clusters makes them ideal for sensing various redox environmental signals, while the physics of iron-sulfur clusters and its host proteins have been long overlooked. One such protein, MagR, has been proposed as a putative animal magnetoreceptor. It forms a rod-like complex with cryptochromes (Cry) and possesses intrinsic magnetic moment. However, the magnetism modulation of MagR remains unknown. Here in this study, iron-sulfur cluster binding in MagR has been characterized. Three conserved cysteines of MagR play different roles in iron-sulfur cluster binding. Two forms of iron-sulfur clusters binding have been identified in pigeon MagR and showed different magnetic properties: [3Fe-4S]-MagR appears to be superparamagnetic and has saturation magnetization at 5 K but [2Fe-2S]-MagR is paramagnetic. While at 300 K, [2Fe-2S]-MagR is diamagnetic but [3Fe-4S]-MagR is paramagnetic. Together, the different types of iron-sulfur cluster binding in MagR attribute distinguished magnetic properties, which may provide a fascinating mechanism for animals to modulate the sensitivity in magnetic sensing.

Impacts of Chemokine (C-X-C Motif) Receptor 2 C1208T Polymorphism on Cancer Susceptibility.

BACKGROUND: The CXC chemokines belong to a unique family of cytokines that participates in the progression and development of many malignant tumors. Evidence for the relationship between chemokine (C-X-C motif) receptor 2 (CXCR2) C1208T polymorphism and susceptibility to cancer remains inconsistent. METHODS: Odds ratios (ORs), 95% confidence intervals (CIs), and combined analysis were used to investigate the effect of CXCR2 variation on cancer risk. Gene Set Enrichment Analysis (GSEA) and enzyme-linked immunosorbent assay (ELISA) were also used to evaluate the expression of CXCR2 in prostate cancer (PCA). RESULTS: Across 11 case-control studies, 4,909 cases and 5,884 controls were involved in the current analysis. Individuals with a TT genotype were associated with increased risk of digestive cancer, compared to those with a TC+CC genotype (OR = 1.16, 95%CI = 1.02-1.31, P = 0.025). Individuals carrying the TT genotype had a 39% higher risk of urinary cancer than those carrying CC genotype (OR = 1.39, 95%CI = 1.04-1.87, P = 0.025). Individuals with a TT genotype showed a 56% augmented breast cancer risk, compared to those with a CC genotype (OR = 1.56, 95%CI = 1.03-2.35, P = 0.034). It was found that CXCR2 expression was downregulated in PCA. Compared with PCA subjects carrying the CC genotype, the expression of CXCR2 was decreased in patients with the TT genotype. CONCLUSIONS: The CXCR2 C1208T variation was associated with elevated risk of urinary, breast, and digestive cancer. However, the C1208T polymorphism was correlated with attenuated risk of lung cancer.

Study of Fe-S Cluster Proteins in Methanococcus maripaludis , a Model Archaeal Organism.

Iron-sulfur (Fe-S) clusters are among the oldest and most versatile cofactors present in all domains of life. Many bacterial and eukaryotic Fe-S proteins have been well-characterized, whereas the archaeal ones are less studied. Fe-S proteins are particularly abundant and play essential roles in methanogenic archaea. Methanococcus maripaludis is a model methanogen with available genetic tools. Here, we describe the techniques for anaerobic cultivation of M. maripaludis with formate, liposome-mediated transformation, expression and anoxic affinity purification of Fe-S proteins, Fe-S cluster reconstitution, and analysis of Fe-S proteins by UV-visible absorption spectroscopy.

Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging.

Age-related skeletal muscle deterioration (sarcopenia) has a significant effect on the elderly's health and quality of life, but the molecular and gene regulatory mechanisms remain largely unknown. It is necessary to identify the candidate genes related to skeletal muscle aging and prospective therapeutic targets for effective treatments. The age-line-related genes (ALRGs) and age-line-related transcripts (ALRTs) were investigated using the gene expression profiles of GSE47881 and GSE118825 from the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) networks were performed to identify the key molecules with Cytoscape, and Gene Set Enrichment Analysis (GSEA) was used to clarify the potential molecular functions. Two hub molecules were finally obtained and verified with quantitative real-time PCR (qRT-PCR). The results showed that the expression of mitochondria genes involved in mitochondrial electron transport, complex assembly of the respiratory chain, tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis were down-regulated in skeletal muscle with aging. We further identified a primary hub gene of CYCS (Cytochrome C) and a key transcription factor of ESRRA (Estrogen-related Receptor Alpha) to be associated closely with skeletal muscle aging. PCR analysis confirmed the expressions of CYCS and ESRRA in gastrocnemius muscles of mice of different ages were significantly different, and decreased gradually with age. In conclusion, the main cause of skeletal muscle aging may be the systematically reduced expression of mitochondrial functional genes. The CYCS and ESRRA may play significant roles in the progression of skeletal muscle aging and serve as potential biomarkers for future diagnosis and treatment.