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2.
Organogenesis ; : 1-15, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806543

RESUMO

Cartilage and joint damage easily degenerates cartilage and turns into osteoarthritis (OA), which seriously affects human life and work, and has no cure currently. The temporal and spatial changes of multiple microenvironments upon the damage of cartilage and joint are noticed, including the emergences of inflammation, bone remodeling, blood vessels, and nerves, as well as alterations of extracellular and pericellular matrix, oxygen tension, biomechanics, underneath articular cartilage tissues, and pH value. This review summarizes the existing literatures on microenvironmental changes, mechanisms, and their negative effects on cartilage regeneration following cartilage and joint damage. We conclude that time-dependently rebuilding the multiple normal microenvironments of damaged cartilage is the key for cartilage regeneration after systematic studies for the timing and correlations of various microenvironment changes.

3.
Mitochondrial DNA B Resour ; 6(12): 3340-3342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746408

RESUMO

Yishui Lily 140 (Lilium lancifolium) is a hybrid lily species which was bred from wild lily varieties due to its edible and medicinal value. In this study, we have sequenced the complete chloroplast (cp) of L. lancifolium. The complete cp sequence is 152,643 bp long, with a large single copy (LSC) region of 82,084 bp, a small single copy (SSC) region of 17,513 bp, and two inverted repeat (IR) regions of 26,492 bp each. The GC contents of the complete cp genomes are 37.0%. It contains 132 genes, including 86 coding genes, 8 ribosomal RNAs, and 38 transfer RNAs. Among them, 16 different genes have a single intron and the remaining two genes have double introns, including nine cis-splicing and one trans-splicing genes. Compared with other species, we found three high variation hot spots and 96 repeats sequence. The genetic information of Lilium can be enriched as well as identifying proximal species. They are edible and have medicinal value for humans. Therefore, sequencing of Yishui Lily 140 is important to explore the cp genome composition.

4.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5320-5329, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738436

RESUMO

In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)-based liver metabolomics approach was used to explore the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in improving atherosclerosis(AS) of mice with apolipoprotein E gene knockout(ApoE~(-/-)). AS mouse model was induced by high-fat diet. The pathological and biochemical indexes such as the histopathological changes, body weight, liver weight, blood lipid level and inflammatory factors in the liver of mice were determined. The metabolic profiling of mice liver samples was performed with UPLC-Q-TOF-MS. Multiple statistical analysis methods including partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to screen and identify biomarkers. The levels of related enzymes including LCAT, sPLA2, EPT1 and ACER1 were detected. The results showed that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" significantly reduced the areas of aortic plaque and fat vacuoles of liver in AS mice and decreased the accumulation of lipid droplets and liver coefficient. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" also regulated the levels of blood lipid and inflammatory injury in the liver. The metabolites of the control group, the model group and the "Trichosanthis Fructus-Allii Macrostemonis Bulbus" group could be distinguished significantly. Fifteen potential biomarkers related to AS were discovered and preliminarily identified, seven of which could be regulated by "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in a trend of returning to normal. Metabolic pathway analysis screened out two major metabolic pathways. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" obviously regulated the levels of LCAT, sPLA2, EPT1 and ACER1. It was inferred that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" could play a major role in AS treatment by regulating glycerophospholipid and sphingolipid metabolism disorders in the liver, with the mechanism probably relating to the intervention of the expression of LCAT, sPLA2, EPT1 and ACER1.


Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Cromatografia Líquida de Alta Pressão , Fígado , Metabolômica , Camundongos
5.
Comput Intell Neurosci ; 2021: 2993870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603429

RESUMO

Today, the global exchange market has been the world's largest trading market, whose volume could reach nearly 5.345 trillion US dollars, attracting a large number of investors. Based on the perspective of investors and investment institutions, this paper combines theory with practice and creatively puts forward an innovative model of double objective optimization measurement of exchange forecast analysis portfolio. To be more specific, this paper proposes two algorithms to predict the volatility of exchange, which are deep learning and NSGA-II-based dual-objective measurement optimization algorithms for the exchange investment portfolio. Compared with typical traditional exchange rate prediction algorithms, the deep learning model has more accurate results and the NSGA-II-based model further optimizes the selection of investment portfolios and finally gives investors a more reasonable investment portfolio plan. In summary, the proposal of this article can effectively help investors make better investments and decision-making in the exchange market.


Assuntos
Aprendizado Profundo , Algoritmos , Investimentos em Saúde
6.
Zhen Ci Yan Jiu ; 46(10): 880-4, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34698464

RESUMO

OBJECTIVE: To observe the effect of auriculotherapy with miniature bian needle on anxious emotion, the condition of angina pectoris attack and sleep quality in the patients with anxiety after percutaneous coronary intervention (post-PCI). METHODS: A total of 74 eligible patients of post-PCI combined with anxious depression were randomized into an auriculotherapy group (37 cases, 2 cases dropped out) and a control group (37 cases, 3 cases dropped out). In the auriculotherapy group, on the base of the conventional secondary prevention medication for coronary heart disease (CHD), auriculotherapy with miniature bian needle was supplemented. In the control group, a proper physical exercise was combined on the base of the secondary prevention medication for CHD. The duration of treatment was 4 weeks in two groups. Separately, the score of Hamilton anxiety scale (HAMA), the score Seattle angina questionnaire (SAQ) and the score of Pittsburgh sleep quality index (PSQI) were assessed in the patients of the two groups before and after treatment. RESULTS: After treatment, the score of HAMA, the score of each item of SAQ and PSQI score were all improved significantly as compared with those before treatment respectively in both the auriculotherapy group and the control group (P<0.001, P<0.05). After treatment, HAMA score, PSQI score and the scores of physical limitation (PL), anginal stability (AS), anginal frequency (AF) and treatment satisfaction (TS) in SAQ in the auriculotherapy group were all better than those in the control group (P<0.001, P<0.05). The total effective rate was 91.43% (32/35) in the auriculotherapy group, obviously higher than 58.82% (20/34) in the control group (P<0.001). CONCLUSION: Auriculotherapy with miniature bian needle effectively relieves anxious emotions and the condition of angina pectrois attack and improves sleep quality in the post-PCI patients with anxiety.


Assuntos
Auriculoterapia , Intervenção Coronária Percutânea , Angina Pectoris/terapia , Ansiedade/terapia , Humanos , Qualidade de Vida , Resultado do Tratamento
7.
Int J Gen Med ; 14: 6755-6767, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703282

RESUMO

Background: Secretome genes, encoding proteins secreted from the cell, are involved in the tumor immune response and correlated with levels of tumor mutation burden (TMB) in multiple tumors. This study aimed to identify core secretome genes and their potential association with immunomodulators and immune infiltration in high TMB groups across 14 major solid tumors through bioinformatics analysis. Methods: Multi-omics data for 14 major solid tumors were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high TMB (TMB-high) and low TMB (TMB-low) groups using the median TMB values for each of the solid tumors. The CIBERSORT algorithm was conducted to estimate the proportion of 22 tumor-infiltrating immune cells (TIICs). Kaplan-Meier analysis and the log-rank test were utilized to screened prognosis-related genes. The correlations between core secretome genes and TIICs were analyzed using Spearman correlation coefficients. Results: In TMB-high groups, multi-omics data analysis revealed that secretome genes were strongly associated with clinical characteristics, and 65 prognosis-related secretome genes were screened. Among the prognosis-related genes, 21 core secretome genes were identified, and strongly associated with five types of TIICs, namely activated NK cells, follicular helper T cells, CD8 T cells, and macrophages M0 and M2. Notably, three secretome genes (ADAMTS12, COL12A1, and COL5A2) were significantly related to immunomodulators and TIICs in multiple solid tumors. In addition, 12 core secretome genes were significantly differentially expressed between responding and non-responding patients receiving immunotherapy. Furthermore, core secretome genes may be involved in the PI3K/AKT signaling pathway. Conclusion: We examined the prognostic significance of secretome genes and their potential association with immunomodulators and immune infiltration across 14 major solid tumors. In summary, three secretome genes (ADAMTS12, COL12A1, and COL5A2) may be pivotal mediators of immune infiltration in TMB-high patients, which may help to identify patients who could benefit from immunotherapy.

8.
J Tradit Chin Med ; 41(5): 789-798, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34708638

RESUMO

OBJECTIVE: To observe the effect of herb-partitioned moxibustion (HPM) on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis (EAT) rats. METHODS: Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, HPM group and western medicine (Med) group. EAT model rats were prepared by a combined immunization with complete and incomplete Freund's adjuvant emulsified with porcine thyroglobulin and iodine. Rats in the HPM group were treated with HPM, while rats in the Med group were treated with levothyrocine (1 µg/2 mL) by gavage. HE staining was used to observe the pathological morphological changes of thyroid tissue, ELISAs was uaed to detect the serum concentrations of TGAb, TPOAb, FT3, FT4, TSH. We then performed high-throughput miRNA sequencing to analyse the miRNA expression profiles in the thyroid tissues, followed by a bioinformatics analysis. RT-qPCR was used to verify the identified differentially expressed miRNAs. RESULTS: HPM improved the thyroid tissue morphology and reduced serum TPOAb, TGAb, TSH concentration in EAT rats (P < 0.05), but with no obvious effect on FT3 and FT4 concentration. While the TSH, FT3 and FT4 concentration was significantly changed in the Med group (P < 0.01 or P < 0.05) compared with that of EAT group. Sequencing results showed that a total of 17 miRNAs were upregulated, and 4 were downregulated in the EAT rats, in which the expression levels of miR-346 and miR-331-5p were reversed by HPM. The target genes of the miRNAs that regulated by HPM were associated with a variety of immune factors and immune signals. RT-qPCR verification showed that the expression of miRNA-346 and miRNA-331-5p was consistent with the sequencing results. CONCLUSIONS: HPM could regulate the the expression of miRNA-346 and miRNA-331-5p, then act on their target genes to immune and inflammation-related pathways, which may be one of the mechanisms of HPM on EAT rats.

9.
Clin Genet ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34595750

RESUMO

Non-obstructive azoospermia (NOA) represents one of the most serious forms of male infertility caused by spermatogenic failure. Despite multiple genes found to be associated with human NOA, the genetic basis of this idiopathic disease remains largely unknown. FBXO43 is a direct inhibitor of the anaphase-promoting complex/cyclosome (APC/C) E3 ligase and crucially important in mouse spermatogenesis. In this study, for the first time, we identified a homozygous nonsense mutation in FBXO43 c.1747C > T:p.Gln583X in two NOA brothers from a Chinese consanguineous family via whole-exome sequencing. FBXO43 was absent from testicular tissue of the proband, and FBXO43-immunostaining signals were invisible in the affected seminiferous tubules. Furthermore, in humans, FBXO43 defects cause meiotic arrest within early diplotene of prophase I. The results here demonstrate the pathogenicity of this loss-of-function mutation and confirmed that spermatocytes were unable to complete meiotic divisions without FBXO43 in humans. In mouse testicular protein extracts, three subunits of the APC/C, including ANAPC2, ANAPC8 and ANAPC10, were validated to interact directly with FBXO43, whereas no interactions were detected for FBXO43 and SKP1. This study furthers our understanding of the genetic basis of human NOA and provides insights into FBXO43 and male infertility.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34657236

RESUMO

PURPOSE: Multiple morphological abnormalities in the sperm flagella (MMAF) comprise a severe phenotype of asthenoteratozoospermia with reduced or absent spermatozoa motility. Whereas dozens of candidate pathogenic genes for MMAF have been identified, the genetic cause in a large proportion of patients is unknown. We attempted to identify novel genetic explanations for MMAF. METHODS: We performed whole-exome sequencing of patients with MMAF to identify pathogenic variants. The phenotypes of spermatozoa in patients carrying DNAH10 variants were investigated using haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy. The expression and location of DNAH10 and other spermatozoa structure-related proteins were analyzed using immunofluorescence assays. RESULTS: We found one homozygous frameshift DNAH10 variant (NM_207437: c.2514delG:p.L839*) and one compound heterozygous DNAH10 variant (NM_207437: c.10820 T > C:p.M3607T; c.12692C > T:p.T4231I) in two patients with MMAF. These variants were absent or rare in the general population. Haematoxylin and eosin staining and scanning electron microscopy revealed the significant disruption of sperm flagella in the patients. In addition, ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella. Using immunofluorescence assays, we found a significant reduction in IDA-related proteins including DNAH10 and DNAH1. CONCLUSIONS: We identified putative novel pathogenic variants in DNAH10 for MMAF, which might advance the genetic diagnosis and clinical genetic counselling for male infertility.

11.
Ecotoxicol Environ Saf ; 227: 112889, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34649140

RESUMO

As the most abundantly used phthalate derivative, di-(2-ethylhexyl) phthalate (DEHP) leads to reproductive disorders, especially in males. Testicular injury can be triggered when the testis is exposed to DEHP during the immature stage. However, the potential mechanism is largely unclear. In the present study, Sprague-Dawley rats were exposed to 0, 250 and 500 mg/kg/day DEHP from postnatal day (PND) 20 to PND 30. The spermatogonia cell line GC-1 and spermatocyte cell line GC-2 were exposed to different doses of monoethylhexyl phthalate (MEHP), a metabolite of DEHP. Testicular injury was observed. Oxidative stress was evaluated both in vivo and in vitro. Our results showed that after DEHP exposure, the testicular structure was damaged and spermatogenesis was disturbed. We also found that oxidative stress was increased, as indicated by the upregulation of the important factors in the antioxidant pathway. Furthermore, the expression of autophagy-related proteins was significantly downregulated. Autophagy inhibition led to activation of the pyroptosis pathway. Nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3), Caspase-1 and cytokine interleukin-1ß (IL-1ß) were significantly upregulated. Additionally, an imbalance in self-renewal and differentiation was observed in germ cells after DEHP exposure, causing the cessation of germ cell development. In summary, these data suggest that DEHP exposure enhances oxidative stress, downregulates autophagy, induces NLRP3 inflammasome activation and subsequently triggers pyroptosis in vivo and in vitro, which provides novel insight into DEHP-related injury in immature testes in the context of pyroptosis.


Assuntos
Dietilexilftalato , Testículo , Animais , Dietilexilftalato/toxicidade , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Transdução de Sinais , Serina-Treonina Quinases TOR
12.
Reprod Sci ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716537

RESUMO

This study investigated whether singleton pregnancies conceived after preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are associated with a higher risk of adverse perinatal outcomes than singleton pregnancies conceived after intracytoplasmic sperm injection (ICSI). We collected data on singleton live births after PGT-SR (n = 107) and ICSI (n = 585) in our hospital from January 2017 to August 2020. Multivariable analyses were used to adjust for maternal age, body mass index, gravidity and parity, paternal age, ovulatory disorder, and recurrent spontaneous abortion. The unadjusted results showed a significantly higher risk of hypertensive disorders of pregnancy (HDP) (odds ratio (OR) = 2.47; 95% confidence interval (CI): 1.10-5.54; P = 0.029) associated with PGT-SR singleton pregnancies than with ICSI singleton pregnancies. However, after adjusting for potential confounders, there were no longer any significant differences in the risk of HDP (adjusted OR = 2.24; 95% CI: 0.92-5.48; P = 0.077) between PGT-SR and ICSI singleton pregnancies. There were no significant differences between PGT-SR and ICSI singleton pregnancies in terms of gestational diabetes, preterm premature rupture of membranes, placenta previa, cesarean delivery, gestational age (weeks), preterm delivery (< 37 weeks), very preterm delivery (≥ 28 weeks and < 32 weeks), birth weight (g), low birth weight (< 2500 g), very low birth weight (< 1500 g), birth height (cm), birth defects, and 1-min and 5-min Apgar scores. In conclusion, for single frozen-thawed blastocyst cycles, there were no significant differences in adverse perinatal outcomes between PGT-SR and ICSI singleton pregnancies. However, due to the limited sample size, these conclusions need to be confirmed by further studies.

13.
BMC Pulm Med ; 21(1): 300, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556069

RESUMO

PURPOSE: Psittacosis is a zoonotic infectious disease caused by the transmission of the bacterium Chlamydia psittaci (C. psittaci) from birds to humans. Infections in humans mainly present as community-acquired pneumonia (CAP). However, most cases are treated without diagnostic testing, and the importance of Chlamydia psittaci infection as a cause of CAP is therefore unclear. Diagnostic tools, including culture, serologic test, and PCR-based methods, are available but prone to false negative results. Metagenomic next-generation sequencing (mNGS) has been increasingly used in the diagnosis of infectious diseases, particularly when conventional diagnostic approaches have limitation. Detection of nucleic acid sequence of C. psittaci in respiratory tract samples by metagenomic next-generation sequencing (mNGS) is effective for early diagnosis of severe C. psittaci pneumonia. Timely treatment based on tetracycline can reduce unnecessary use of antibiotics and improve prognosis of patients with severe C. psittaci pneumonia. METHODS: Clinical data of thirteen patients with severe C. psittaci pneumonia diagnosed by mNGS were collected. Clinical manifestations, treatment and prognosis of patients were summarized. RESULTS: The typical symptoms of pneumonia caused by C. psittaci include fever, headache, myalgia, cough, and dyspnea. In the current study, all patients met the criteria for severe C. psittaci pneumonia and received mechanical ventilation, including noninvasive mechanical ventilation (five/thirteen) and invasive mechanical ventilation (eight/thirteen). The findings showed that patients with C. psittaci pneumonia presented with normal or slightly increased leucocytes and procalcitonin, and high C-reactive protein levels. Computed tomography manifestations included consolidation of lung parenchyma, with air bronchogram and pleural effusion in some patients. mNGS analysis results were obtained within 48-72 h. Eleven patients fully recovered after targeted treatment, however, two patients died from secondary multidrug-resistant Pseudomonas aeruginosa infection. CONCLUSIONS: The findings of the current study show that mNGS is effective in diagnosis of C. psittaci pneumonia, and has significant diagnosis value in patients with severe infection. Patients responds well to the timely use of appropriate antibiotics.

14.
Zhongguo Zhen Jiu ; 41(9): 1055-9, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491658

RESUMO

OBJECTIVE: To analyze the literature of acupuncture and moxibustion for diseases in the recent 5 years, and discuss the spectrum and indications of acupuncture and moxibustion. METHODS: The literature on acupuncture and moxibustion for diseases in CNKI, Wanfang and VIP databases from January 1, 2015 to December 31, 2019 was searched, summarized and analyzed, and the disease spectrum was summarized. At the same time, the literature from 2015 to 2019 (group A), 1978 to 2005 (group B), and 1949 to 2005 (group C) was compared, and the indications of acupuncture and moxibustion therapy were summarized. RESULTS: There were 32 011 articles on acupuncture and moxibustion for diseases in the recent 5 years, including 377 kinds of indications. These indications can be mostly classified as neurology (9384), orthopedics and traumatology (7765), gastroenterology (3529) and obstetrics and gynecology (2283). The types of diseases were mostly gastroenterology (52 types), neurology (47 types), ophthalmology and otorhinolaryngology (47 types), and obstetrics and gynecology (42 types). The first-class indications of acupuncture and moxibustion therapy in the recent 5 years were hemiplegia, lumbar disc herniation, cervical spondylosis, knee osteoarthritis, insomnia, constipation and cerebrovascular diseases; the second-class were facial neuritis, shoulder pain and headache; the third-class were dysphagia, dysmenorrhea and depression; the forth-class were asthma, urinary retention, cerebral palsy, hypertension, dementia, side effects of radiotherapy and chemotherapy, infertility, allergic rhinitis, vertigo, shoulder-hand syndrome, diabetic neuropathy, herpes zoster, pain, hiccup, diarrhea, lumbar sprain and sciatica. CONCLUSION: Although the disease spectrum and indications of acupuncture and moxibustion therapy have changed to some extent in the recent 5 years, neurology and orthopedics and traumatology are still predominant, and the observation objects tend to transition from symptoms to diseases.


Assuntos
Terapia por Acupuntura , Acupuntura , Moxibustão , Bibliometria , Dismenorreia , Feminino , Humanos
15.
Chin Med J (Engl) ; 134(18): 2205-2213, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34553702

RESUMO

BACKGROUND: Hyperbaric oxygen treatment (HBOT) has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids. To explore the mechanism of the effect of HBOT on keloids, tumor immune gene expression and immune cell infiltration were studied in this work. METHODS: From February 2021 to April 2021, HBOT was carried out on keloid patients four times before surgery. Keloid tissue samples were collected and divided into an HBOT group (keloid with HBOT before surgery [HK] group, n = 6) and a non-HBOT group (K group, n = 6). Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit. Data were mined with R package. The differentially expressed genes between the groups were compared. Hub genes between the groups were determined and verified with Quantitative Real-time PCR. Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry (IHC). RESULTS: Inflammatory cell infiltration was reduced in the HK group. There were 178 upregulated genes and 217 downregulated genes. Ten hub genes were identified, including Integrin Subunit Alpha M (ITGAM), interleukin (IL)-4, IL-6, IL-2, Protein Tyrosine Phosphatase Receptor Type C (PTPRC), CD86, transforming growth factor (TGF), CD80, CTLA4, and IL-10. CD80, ITGAM, IL-4, and PTPRC with significantly downregulated expression were identified. IL-10 and IL-2 were upregulated in the HK group but without a significant difference. Infiltration differences of CD8 lymphocyte T cells, CD4 lymphocyte T-activated memory cells, and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis. Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification. CONCLUSION: HBOT affected tumor gene expression and immune cell infiltration in keloids. CD4 lymphocyte T cell, especially activated memory CD4+T, might be the key regulatory immune cell, and its related gene expression needs further study.


Assuntos
Oxigenação Hiperbárica , Queloide , Neoplasias , Expressão Gênica , Humanos , Queloide/genética , Queloide/terapia , Oxigênio
16.
Clin Genet ; 100(6): 731-742, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34569065

RESUMO

Reduced generation of multiple motile cilia (RGMC) and the consequent primary ciliary dyskinesia (PCD) cause infertility due to a substantial reduction in the number of multiciliated cells (MCCs) in the efferent ducts (EDs)/oviducts. MCIDAS acts upstream of CCNO to regulate the biogenesis of basal bodies (BBs); therefore, both genes play a vital role in the multiciliogenesis of the reproductive tract epithelium. In this study, whole-exome sequencing was performed to identify the causative genes in 10 unrelated infertile patients with PCD: seven males and three females. Notably, homozygous frameshift mutations in MCIDAS (c.186dupT, p.Pro63Serfs*22) and CCNO (c.262_263insGGCCC, p.Gln88Argfs*8) were identified in one male and one female participant from two unrelated consanguineous families. Haematoxylin-eosin staining/scanning electron microscopy revealed abnormal MCCs in the mutated EDs/oviducts. Furthermore, transmission electron microscopy revealed significantly reduced BBs. Immunofluorescence staining showed the absence of MCIDAS and CCNO signals in the affected tissues and confirmed that MCIDAS acts upstream of CCNO in the context of multiciliogenesis in the reproductive tract epithelium. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was successful, with a positive pregnancy outcome in both MCIDAS- and CCNO-mutated patients. Our results support the use of IVF/ICSI interventions to treat infertility due to RGMC in couples.

17.
Front Genet ; 12: 715339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394199

RESUMO

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy affecting the cilia and sperm flagella. Mutations in genes related to the structural and functional defects of respiratory ciliary axoneme have been reported to be the predominant cause of this symptom; however, evidence regarding male infertility and genotype-phenotype associations between some of these genes and flagellar axoneme remains unclear. Here, we reported a male patient from a non-consanguineous Chinese family who exhibited left/right body asymmetry and oligoasthenoterazoospermia factor infertility. Novel compound heterozygous mutations in ARMC4 (NM:018076: c.2095C>T: p. Gln699*; c.1679C>T: p. Ala560Val) were identified in this patient, and his parents were a heterozygous carrier for the mutations. Morphological and ultrastructural analysis of the spermatozoa from the man showed aberrant sperm flagella with axonemal disorganization and outer dynein arm (ODA) loss. In addition, immunofluorescence analysis of the spermatozoa from the proband and a control man revealed a significant lower expression of ARMC4 protein due to pathogenic mutations. Therefore, our findings help to expand the spectrum of ARMC4 pathogenic mutations and linked biallelic ARMC4 mutations to male infertility for the first time.

18.
Endocrinology ; 162(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34338758

RESUMO

The blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), which are synchronized through the crosstalk of Sertoli cells and Sertoli germ cells, are required for spermatogenesis and sperm release. Here, we show that Wnt5a, a noncanonical Wnt signaling pathway ligand, is predominately expressed in both the BTB and apical ES and has a specific expression pattern during the seminiferous epithelium cycle. We employed siRNA to knockdown Wnt5a expression in testis and Sertoli cells, and then identified elongated spermatids that lost their polarity and were embedded in the seminiferous epithelium. Moreover, phagosomes were found near the tubule lumen. These defects were due to BTB and apical ES disruption. We also verified that the expression level and/or location of BTB-associated proteins, actin binding proteins (ABPs), and F-actin was changed after Wnt5a knockdown in vivo and in vitro. Additionally, we demonstrated that Wnt5a regulated actin dynamics through Ror2-mediated mTORC1 and mTORC2. This study clarified the molecular mechanism of Wnt5a in Sertoli cell junctions through the planar cell polarity (PCP) signaling pathway. Our findings could provide an experimental basis for the clinical diagnosis and treatment of male infertility caused by Sertoli cell junction impairment.

19.
Environ Pollut ; 289: 117904, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371264

RESUMO

It has been found that polystyrene microplastics (PS-MPs) exposure leads to decreased sperm quality and quantity, and we aim to explore the underlying mechanisms. Therefore, we gave 20 mg/kg body weight (bw) and 40 mg/kg bw 4 µm and 10 µm PS-MPs to male Balb/c mice by gavage. RNA sequencing of testes was performed. After PS-MPs exposure, blood-testis barrier (BTB) integrity was impaired. Since cytoskeleton was closely related to BTB integrity maintenance, and cytoskeleton disorganization could be induced by PS-MPs exposure in the testis, which resulted in the truncation of actin filaments and disruption of BTB integrity. Such processes were attributed to the differential expression of Arp3 and Eps8 (two of the most important actin-binding proteins). According to the transcriptome sequencing results, we examined the oxidative stress level in the testes and Sertoli cells. We found that PS-MPs exposure induced increased reactive oxygen species (ROS) level, which destroyed the balance between mTORC1 and mTORC2 (the mTORC1 activity was increased, while the mTORC2 activity was decreased). In conclusion, PS-MPs induced the imbalance of mTORC1 and mTORC2 via the ROS burst, and altered the expression profile of actin-binding proteins, resulting in F-actin disorganization and reduced expression of junctional proteins in the BTB. Eventually PS-MPs led to BTB integrity disruption and spermatogenesis dysfunction.


Assuntos
Barreira Hematotesticular , Microplásticos , Animais , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Plásticos , Poliestirenos , Espécies Reativas de Oxigênio , Espermatogênese
20.
Orthop Surg ; 13(6): 1890-1898, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34431625

RESUMO

OBJECTIVE: To describe the secular trends in comorbidities and postoperative complications of geriatric hip fracture patients from the Chinese People's Liberation Army General Hospital Hip Fracture Cohort between 2000 and 2019. METHODS: We included 2,805 hip fracture patients aged 65 years or older and received surgical treatment from 25 January 2000 to 19 December 2019. Demographic characteristics, comorbidities, postoperative complications, length of hospital stay, and the time to surgery were extracted and examined in each 5-year period based on the admission year, namely 2000-2004, 2005-2009, 2010-2014, and 2015-2019. Categorical data were analyzed by chi-squared or Fisher's exact test, with ordinal data by row mean scores difference test and continuous data by one-way analysis of variance. Trends in comorbidities and postoperative complications were examined by the Cochran-Armitage trend test. RESULTS: The average age of the included population was 79.1 ± 7.3 years (mean ± standard deviation), and 69.1% were female. From 2000 to 2019, the proportion of females increased from 59.8% to 73.0% (P for trend <0.05). Hypertension (51.8%), type 2 diabetes (23.6%), coronary heart disease (20.9%), stroke (18.7%), and arrhythmia (11.2%) were the most prevalent five comorbidities. The proportion of hypertension was 27.0%, 45.4%, 53.0%, and 57.2% in each 5-year period with an increasing trend (P for trend <0.05). The proportion of type 2 diabetes was 9.8%, 22.8%, 23.5%, and 26.0% in each 5-year period (P for trend <0.05). Similar increasing trends were found in myocardial infarction, arrhythmia, and tumor. On the contrary, the proportion of patients with major postoperative complications decreased from 2000 to 2019, with 23.0%, 14.6%, 6.5%, and 5.6% in each 5-year period (P for trend <0.05). For each specific postoperative complication, i.e. pneumonia, cardiovascular event, respiratory failure, and in-hospital death, similar decreasing trends were found (all P for trend <0.05). CONCLUSION: This descriptive analysis sheds light on the fact that the health status of the hip fracture population tends to shift gradually. Improving concepts and practices of clinical interventions may help reduce postoperative complications, whereas challenges in the management of comorbidities increase.


Assuntos
Comorbidade/tendências , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fixação de Fratura/métodos , Humanos , Masculino , Centros de Atenção Terciária
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