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1.
Genomics Proteomics Bioinformatics ; 20(2): 350-365, 2022 04.
Article in English | MEDLINE | ID: mdl-34974191

ABSTRACT

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable confounding effects, and recapitulate age-dependent changes in the gut microbiota of healthy primates. Herein we performed 16S rRNA gene sequencing, characterized the age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed the lifelong dynamic changes of the primate gut microbiota. While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium, the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants, underlining their potential role in host development. Importantly, topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity, and its tremendous decline with age could probably be linked to healthy aging. Moreover, we identified key driver microbes responsible for such age-dependent network changes, which were further linked to altered metabolic functions of lipids, carbohydrates, and amino acids, as well as phenotypes in the microbial community. The current study thus demonstrates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota, and provides new insights into their roles in the development and healthy aging of their hosts.


Subject(s)
Gastrointestinal Microbiome , Healthy Aging , Microbiota , Humans , Infant , Animals , Aged , RNA, Ribosomal, 16S/genetics , Haplorhini/genetics
2.
Biochem Biophys Res Commun ; 531(2): 172-179, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32788070

ABSTRACT

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP), in which exon open reading frame 15 (ORF15) of RPGR has been implicated to play a substantial role. We identified a novel hemizygous missense mutation E585K of RPGR from whole-exome sequencing of RP. RNA-Seq analysis and functional study were conducted to investigate the underlying pathogenic mechanism of the mutation. Our results showed that the mutation actually affected RPGR ORF15 splicing. RNA-Seq analysis of the human retina followed by validation in cells revealed a complex splicing pattern near the 3' boundary of RPGR exon 14 in the ORF15 region, resulting from a variety of alternative splicing events (ASEs). The wildtype RPGR mini-gene expressed in human 293T cells confirmed these ASEs in vitro. In contrast, without new RNA species detected, the mutant mini-gene disrupted the splicing pattern of the ORF15 region, and caused loss of RPGR transcript heterogeneity. The RNA species derived from the mutant mini-gene were predominated by a minor out-of-frame transcript that was also observed in wildtype RPGR, resulting from an upstream alternative 5' splice site in exon 14. Our findings therefore provide insights into the influence of RPGR exonic mutations on alternative splicing of the ORF15 region, and the underlying molecular mechanism of RP.


Subject(s)
Eye Proteins/genetics , Mutation, Missense/genetics , Open Reading Frames/genetics , Retinitis Pigmentosa/genetics , Amino Acid Sequence , Base Sequence , Cell Line , Eye Proteins/chemistry , Hemizygote , Humans , Male , RNA Splicing/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism
3.
J Pak Med Assoc ; 70(12(B)): 2472-2475, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33475568

ABSTRACT

Symptomatic spinal epidural haematoma (SSEH) is a rare but serious postoperative complication. This study aimed to assess the prevalence, causes and treatment of SSEH after adult spinal deformity (ASD) surgery. The patients admitted from August 2012 till August 2016 were retrospectively reviewed using case notes. During these four years, 102 patients were admitted with adult spinal deformity, out of which 3 (2.9%) developed post-operative SSEH. The duration between surgery to onset of SSEH was 10-13 hours (average 11.7 hours) post-operatively. Three patients were treated by haematoma evacuation at 8.5-14 hour (average 11.4 hours) after the symptoms appeared. One patient had improved by 2 Frankel grades, and two patients had improved by1 Frankel grade at the last followup. The results concluded that post-operative SSEH occurred in 2.9% of ASD patients who underwent corrective spinal procedures. Improvement in neurological deficits can be achieved by early haematoma evacuation.


Subject(s)
Hematoma, Epidural, Spinal , Adult , Hematoma, Epidural, Spinal/diagnostic imaging , Hematoma, Epidural, Spinal/epidemiology , Hematoma, Epidural, Spinal/etiology , Humans , Magnetic Resonance Imaging , Neurosurgical Procedures , Postoperative Period , Retrospective Studies , Spine
4.
Zhonghua Wei Chang Wai Ke Za Zhi ; 15(7): 706-9, 2012 Jul.
Article in Chinese | MEDLINE | ID: mdl-22851075

ABSTRACT

OBJECTIVE: To explore the clinical value of 64-slice spiral 3-phase CT enhanced scanning for preoperative TNM staging assessment of gastric carcinoma. METHODS: A retrospective study was performed to review the 64-slice spiral 3-phase CT enhanced scanning of 120 patients with gastric cancer diagnosed by biopsy prior to operation and postoperative pathological reports. All the findings were reviewed by two senior radiologic diagnosticians separately and compared with pathological findings. RESULTS: The accuracy of 64-slice spiral CT enhanced scan was 79.2%(95/120) for T staging, 66.7%(10/15) for T1, 66.7%(14/21) for T2, 84.0%(42/50) for T3, and 85.3%(29/34) for T4. For gastric wall with single layer and multiple layers, the accuracy of CT enhanced scanning was 59.4%(19/32) and 81.8%(72/88) for T staging, and the difference was statistically significant(P<0.05). The accuracy of 64-slice spiral CT enhanced scan was 73.9%(85/115) for N staging, 75.5%(37/49) for N0, 70.3%(26/37) for N1, 75.9%(22/29) for N2. The accuracy of 64-slice spiral CT enhanced scanning was 89.2% for M staging. CONCLUSION: 64-slice spiral CT 3-phase enhanced scanning can monitor the invasion, lymphatic metastasis, and distant metastasis of gastric cancer dynamically, which may become an important examination item for the preoperative evaluation of gastric cancer.


Subject(s)
Stomach Neoplasms/diagnostic imaging , Tomography, Spiral Computed/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/pathology
5.
Sheng Li Ke Xue Jin Zhan ; 43(2): 89-95, 2012 Apr.
Article in Chinese | MEDLINE | ID: mdl-22774635

ABSTRACT

Aquaporins (AQPs), mainly distributed in epithelial and endothelial cells, are a family of channel-forming membrane proteins, originally confirmed to mediate the cellular water-transportation. AQPs are essential for maintaining homeostasis of the body water. Recently, studies have shown that AQPs may be involved in vascular function regulation and the development of related diseases, especially in cerebral ischemia, congestion heart failure, hypertension and tumor angiogenesis. Therefore, further studies are needed to elucidate mechanism accounting for the association between AQPs and vascular function related diseases, which may lead to novel approaches to the prevention and treatment of these diseases. In this review, we will discuss the expression and physiological roles of AQPs in vascular tissues and summarize recent progress in the relationship between AQPs and vascular function related diseases.


Subject(s)
Aquaporins/physiology , Blood Vessels/physiology , Brain Ischemia/physiopathology , Neoplasms/blood supply , Neovascularization, Pathologic/physiopathology , Animals , Endothelium, Vascular/physiology , Heart Failure/physiopathology , Humans
6.
Cell Physiol Biochem ; 29(3-4): 583-94, 2012.
Article in English | MEDLINE | ID: mdl-22508065

ABSTRACT

BACKGROUND/AIMS: Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens. The present study was designed to determine the protective effect of Ganoderma lucidum polysaccharide (Gl-PS) on diabetic wound healing and investigate underlying mechanisms. METHODS: Streptozotocin (STZ)-induced type 1 diabetic mice with full-thickness excisional wounds were intragastrically administered with 10, 50 or 250 mg/kg/day of Gl-PS. RESULTS: Gl-PS dose-dependently rescued the delay of wound closure in diabetic mice. 50 and 250 mg/kg/day of Gl-PS treatment significantly increased the mean perfusion rate around the wound in diabetic mice. Diabetic conditions markly increased mitochondrial superoxide anion (O(2)·(-)) production, nitrotyrosine formation, and inducible nitric oxide synthase (iNOS) activity in wound tissues, which were normalized with Gl-PS treatment. In diabetic wound tissues, the protein level of manganese superoxide dismutase (MnSOD) was unchanged whereas MnSOD activity was inhibited and its nitration was potentiated; Gl-PS administration suppressed MnSOD nitration and increased MnSOD and glutathione peroxidase (GPx) activities. Moreover, Gl-PS attenuated the redox enzyme p66Shc expression and phosphorylation dose-dependently in diabetic mice skin. CONCLUSION: Gl-PS rescued the delayed wound healing and improved wound angiogenesis in STZ-induced type 1 diabetic mice, at least in part, by suppression of cutaneous MnSOD nitration, p66Shc and mitochondrial oxidative stress.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Oxidative Stress , Polysaccharides/therapeutic use , Reishi/chemistry , Wound Healing , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/pathology , Dose-Response Relationship, Drug , Glutathione Peroxidase/metabolism , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Male , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Nitric Oxide Synthase Type II/metabolism , Polysaccharides/administration & dosage , Shc Signaling Adaptor Proteins/metabolism , Skin/drug effects , Skin/injuries , Skin/metabolism , Skin/pathology , Src Homology 2 Domain-Containing, Transforming Protein 1 , Streptozocin/administration & dosage , Streptozocin/adverse effects , Superoxide Dismutase/metabolism , Tyrosine/analogs & derivatives , Tyrosine/metabolism
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