Genetically predicted high sex hormone binding globulin was associated with decreased risk of polycystic ovary syndrome.

BACKGROUND: Previous observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary syndrome (PCOS). Nevertheless, conventional observational studies may be susceptible to bias. Consequently, we conducted a two-sample Mendelian randomization (MR) investigation to delve deeper into the connection between SHBG levels and the risk of PCOS. METHODS: We employed single-nucleotide polymorphisms (SNPs) linked to serum SHBG levels as instrumental variables (IVs). Genetic associations with PCOS were derived from a meta-analysis of GWAS data. Our primary analytical approach relied on the inverse-variance weighted (IVW) method, complemented by alternative MR techniques, including simple-median, weighted-median, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) testing. Additionally, sensitivity analyses were conducted to assess the robustness of the association. RESULTS: We utilized 289 SNPs associated with serum SHBG levels, achieving genome-wide significance, as instrumental variables (IVs). Our MR analyses revealed that genetically predicted elevated circulating SHBG concentrations were linked to a reduced risk of PCOS (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.39-0.78, P = 8.30 × 10-4) using the IVW method. MR-Egger regression did not detect any directional pleiotropic effects (P intercept = 0.626). Sensitivity analyses, employing alternative MR methods and IV sets, consistently reaffirmed our results, underscoring the robustness of our findings. CONCLUSIONS: Through a genetic epidemiological approach, we have substantiated prior observational literature, indicating a potential causal inverse relationship between serum SHBG concentrations and PCOS risk. Nevertheless, further research is needed to elucidate the underlying mechanism of SHBG in the development of PCOS.

Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy.

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

CELLULAR SENESCENCE IMPLICATED IN SEPSIS-INDUCED MUSCLE WEAKNESS AND AMELIORATED WITH METFORMIN.

ABSTRACT: Background: Sepsis is a life-threatening medical emergency, frequently complicated with intensive care unit-acquired weakness syndrome (ICU-AW). ICU-AW patients display flaccid weakness of the limbs, especially in the proximal limb muscles. However, little is known regarding its pathogenesis. Here, we aimed to identify the potential signaling pathway involved in ICU-AW regulation and identify a potential therapeutic drug for intervention. Methods: Both in vivo and in vitro septic mice were used. For the in vivo septic mice, either cecum ligation and puncture or intraperitoneal injection of LPS was conducted in mice. The body weight and muscle mass were then measured and recorded. Muscle strength was evaluated by limb grip strength test. The expression of proteins extracted from cells and muscles was checked through Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was carried out to test the transcriptional level of genes. Senescence-associated ß-galactosidase (SA-ß-gal) staining and Sirius red for collagen staining were conducted. Metformin, as an antiaging agent, was then tested for any attenuation of sepsis-related symptoms. For in vitro sepsis modeling, myoblasts were treated with LPS, analyzed for senescence-related protein expression, and subsequently retested upon metformin treatment. Results: We found that both the weight and strength of muscle were dramatically reduced in cecum ligation and puncture- or LPS-induced septic mice. RNA-seq analysis revealed that various cellular senescent genes were involved in sepsis. In line with this, expression of senescence-related genes, p53 and p21 were both upregulated. Both SA-ß-gal and Sirius red for collagen staining were enhanced in tibialis anterior muscles. Notably, inhibition of p53 expression by siRNA prominently reduced the number of SA-ß-gal-positive myoblasts upon LPS treatment. This indicated sepsis-induced cellular senescence to be dependent on p53. Consistent with the function of metformin in antiaging, metformin attenuated cellular senescence in both murine myoblasts and skeletal muscles during sepsis. Muscle strength of septic mice was improved upon metformin treatment. Metformin intervention is therefore proposed as a potential therapeutic strategy for ICU-AW. Conclusion: Taken together, we revealed a previously unappreciated linkage between cellular senescence and sepsis-induced muscle weakness and propose metformin as a potential therapeutic drug for the treatment of ICU-AW.

[Research progress in chemical constituents, pharmacological activity, and quality markers of Bruceae Fructus].

Bruceae Fructus is a Chinese herbal medicine with the chemical constituents mainly including Brucea javanica oil, quassinoids, flavonoids, steroids, triterpenoids, and alkaloids. Modern research demonstrates that Bruceae Fructus has anti-tumor, anti-malaria, anti-inflammatory, and lipid-lowering activities. This paper introduces the resource distribution, chemical constituents, and pharmacological activities of Bruceae Fructus. Further, according to the concept of quality marker(Q-marker), this paper predicts the Q-markers of Bruceae Fructus from the specificity of chemical components, pharmaceutical activity, measurability of chemical constituents, compatibility, and clinical efficacy, aiming to provide a theoretical basis for establishing the quality standard of Bruceae Fructus.

Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes.

As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive. Here, we found that the C-terminus of IRS-1 undergoes liquid-liquid phase separation (LLPS). Both electrostatic and hydrophobic interactions were seen to drive IRS-1 LLPS. Self-association of IRS-1, which was mainly mediated by the 301-600 region, drives IRS-1 LLPS to form insulin/IGF-1 signalosomes. Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases.

KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming.

Translational reprogramming is part of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, which acts to the advantage of cancer growth and development in different stress conditions, but the mechanism of ER stress-related translational reprogramming in colorectal carcinoma (CRC) progression remains unclear. Here, we identified that Krüppel-like factor 16 (KLF16) can promote CRC progression and stress tolerance through translational reprogramming. The expression of KLF16 was upregulated in CRC tissues and associated with poor prognosis for CRC patients. We found that ER stress inducers can recruit KLF16 to the nucleolus and increase its interaction with two essential proteins for nucleolar homeostasis: nucleophosmin1 (NPM1) and fibrillarin (FBL). Moreover, knockdown of KLF16 can dysregulate nucleolar homeostasis in CRC cells. Translation-reporter system and polysome profiling assays further showed that KLF16 can effectively promote cap-independent translation of ATF4, which can enhance ER-phagy and the proliferation of CRC cells. Overall, our study unveils a previously unrecognized role for KLF16 as an ER stress regulator through mediating translational reprogramming to enhance the stress tolerance of CRC cells and provides a potential therapeutic vulnerability.

[Efficacy and safety of body-insulated acupuncture needle for electrical stimulation at rabbit scia-tic nerve trunk].

OBJECTIVE: To evaluate the efficacy and safety of electrical stimulation at the rabbit sciatic nerve trunk with the body-insulated acupuncture needle whose body is painted with insulating material. METHODS: Eighteen male New Zealand rabbits were randomized into the body-insulated acupuncture needle (BIAN), the general acupuncture needle (GAN), and the blank control groups，with 6 rabbits in each group. The rats'sciatic nerve trunks in BIAN and GAN groups were stimulated by electroacupuncture with the body-insulated acupuncture needle (only allowing the uncoated needle handle and tip to conduct electricity) and the general acupuncture needle, separately. The current intensity was recorded when regular plantarflexion reflexes (sciatic nerve effector reflexes) were observed in the rabbit's foot. The pathological changes of the sciatic nerve at the acupuncture site were observed by H.E. staining, and the ultrastructural changes of the sciatic nerve trunk were observed by transmission electron microscope. RESULTS: The intensity of the current causing the regular plantar flexion reflection in BIAN group (ï¼»0.29±0.07ï¼½ mA) was significantly lower than that in the GAN group(ï¼»0.86±0.08ï¼½ mA, P<0.01). H.E. staining revealed nerve axon degeneration, forming eosinophilic bodies, nerve fiber edema, and focal loss of myelin sheath in the GAN group. While the nerve fiber damage was not obvious, and axons were only degenerated in a few areas in the BIAN group. Transmission electron microscopy observations showed that the nerve myelin sheath structure was separated, the layers were arranged disorderly and bubbled in the GAN group. while the nerve myelin sheath structure of the BIAN group was normal, and it presents a concentric circle-like light and dark lamellar structure, with fewer myelin vacuoles and fissures, only a small part of the mitochondria, microfilaments, and microtubules of the nerve axons were abnormal, and the overall vacuole-like degeneration was significantly reduced, with few of the myelinated fibers were slightly degenerated, and axonal disease was not obvious. CONCLUSION: Insulated acupuncture needle is more accurate and safer than ordinary acupuncture needle for electrical stimulation of rabbit sciatic nerve trunk, and the required electric current intensity is smaller.

Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients.

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

Fabrication and Characterization of Silk Fibroin/Curcumin Sustained-Release Film.

In the present work, a sustained-release film composed of silk fibroin (SF), curcumin (Cur), glutaraldehyde (GA), and glycerol (Gly) was prepared successfully for wound dressings. Features relevant to wound dressings of SF/Gly/GA/Cur film were assessed. Physical and chemical properties of the fabricated materials were also characterized. The results showed that the prepared SF/Gly/GA/Cur film demonstrated a good sustained-release performance, flexibility, and gas permeability. In addition, it was found that the prepared SF/Gly/GA/Cur film possessed the capability to effectively inhibit the growth of bacteria and prevent bacterial penetration with a suitable water vapor transmission rate. Furthermore, the prepared composite film was non-cytotoxic, which makes it an ideal material for wound dressings.

Thiolation and characterization of regenerated Bombyx mori silk fibroin films with reduced glutathione.

Bombyx mori silk fibroin-based materials have good biocompatibility and biodegradability. In order to maximize their utility while maintain appropriate features, silk fibroin (SF) films were modified with reduced glutathione (GSH) (NH2)-ECG-(COOH), using the carbodiimide chemistry method, for the introduction of thiol groups onto surfaces. The effects of this modification on SF films' chemical and physical properties, and cytotoxicity were assessed. The chemical and elemental composition analysis results suggested that reduced glutathione (GSH) was covalently coupled onto the surface of silk fibroin films. Atomic force microscopy (AFM) results indicated the surface roughness of silk fibroin film was increased after the modification by GSH. The GSH-modified silk fibroin films also showed the smaller contact angle due to the hydrophilic peptides coupled on the film surface. Through MTT assay, it was shown that the chemically modified SF film was not cytotoxic to HEK293 cells, and it had no adverse influence on the growth of HEK293 cells. Our approach provides a new option to engineer SF-based material surface with thiol groups in order to allow for secondary reactions and holds great promise for applications of SF-based materials in the biomedical field.

Hsp90ß interacts with MDM2 to suppress p53-dependent senescence during skeletal muscle regeneration.

Cellular senescence plays both beneficial and detrimental roles in embryonic development and tissue regeneration, while the underlying mechanism remains elusive. Recent studies disclosed the emerging roles of heat-shock proteins in regulating muscle regeneration and homeostasis. Here, we found that Hsp90ß, but not Hsp90α isoform, was significantly upregulated during muscle regeneration. RNA-seq analysis disclosed a transcriptional elevation of p21 in Hsp90ß-depleted myoblasts, which is due to the upregulation of p53. Moreover, knockdown of Hsp90ß in myoblasts resulted in p53-dependent cellular senescence. In contrast to the notion that Hsp90 interacts with and protects mutant p53 in cancer, Hsp90ß preferentially bound to wild-type p53 and modulated its degradation via a proteasome-dependent manner. Moreover, Hsp90ß interacted with MDM2, the chief E3 ligase of p53, to regulate the stability of p53. In line with these in vitro studies, the expression level of p53-p21 axis was negatively correlated with Hsp90ß in aged mice muscle. Consistently, administration of 17-AAG, a Hsp90 inhibitor under clinical trial, impaired muscle regeneration by enhancing injury-induced senescence in vivo. Taken together, our finding revealed a previously unappreciated role of Hsp90ß in regulating p53 stability to suppress senescence both in vitro and in vivo.

Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration.

The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.

Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo.

Cervical cancer is one of the most malignant types of tumor and the fourth leading cause of cancer-associated mortality in females worldwide. High expression of brain cytoplasmic RNA 1 (BCYRN1) has been detected in various tumors. The present study aimed to investigate the effect of BCYRN1 in the viability and motility of cervical cancer, and the relevant mechanism. The results demonstrated that BCYRN1 was upregulated in cervical cancer tissues compared with normal tissues. Elevated levels of BCYRN1 were also detected in three human cervical cancer cell lines (SiHa, HeLa and CaSki) compared with non-cancerous ectocervical epithelial cell line (Ect1/E6E7). The expression of BCYRN1 was suppressed following transfection with small interfering RNA (siRNA) in HeLa cells. The silence of BCYRN1 significantly reduced cell viability and motility. Furthermore, microRNA (miR)-138 was predicted as a direct target of BCYRN1 and the expression of miR-138 was elevated in HeLa cells transfected with BCYRN1 siRNA. Subsequently, elevated levels of miR-138 were suppressed by transfection with miR-138 inhibitor in HeLa cells pretreated with BCYRN1 siRNA. The targeting association between BCYRN1 and miR-138 was supported by luciferase reporter assays. Additionally, BCYRN1 siRNA partially counteracted the effect of miR-138 inhibitor on promoting cell viability and mobility in HeLa cells. Finally, the in vivo experiment verified that BCYRN1 siRNA was able to prevent tumor growth, and reduced the expression of migration marker proteins metalloproteinase 2 and vascular endothelial cell growth factor, with enhanced expression levels of miR-138. These results suggest that lncRNA BCYRN1 promotes the proliferation and invasion of cervical cancer via targeting miR-138.

Protein Interacting C-Kinase 1 Modulates Surface Expression of P2Y6 Purinoreceptor, Actin Polymerization and Phagocytosis in Microglia.

Microglia clean up dead cells and debris through phagocytosis in the central nervous system. UDP-activated P2Y6 receptors (P2Y6Rs) induce the formation of phagocytic cup-like structure and P2Y6R expression is increased during the phagocytosis. However, it remains unclear how surface expression of P2Y6R is increased. PICK1 (protein interacting with C-kinase-1) interacts with various neurotransmitter receptors, transporters, and enzymes. We here report that PICK1 might interact with P2Y6R. Surface P2Y6R was reduced in microglia from PICK1-knockout mice and PICK1-knockdown BV2 cells, which was also confirmed by electrophysiological recordings, showing that P2Y6R-mediated current was increased by PICK1 overexpression but was reduced by PICK1-knockdown in BV2 microglia. Finally, PICK1 was sufficient to affect cytoskeletal aggregation and phagocytosis both in primary microglia and BV2 cells. These results indicate that PICK1 is an important regulator of P2Y6R expression and microglial phagocytosis.

Inactivation and unfolding of protein tyrosine phosphatase from Thermus thermophilus HB27 during urea and guanidine hydrochloride denaturation.

The effects of urea and guanidine hydrochloride (GdnHCl) on the activity, conformation and unfolding process of protein tyrosine phosphatase (PTPase), a thermostable low molecular weight protein from Thermus thermophilus HB27, have been studied. Enzymatic activity assays showed both urea and GdnHCl resulted in the inactivation of PTPase in a concentration and time-dependent manner. Inactivation kinetics analysis suggested that the inactivation of PTPase induced by urea and GdnHCl were both monophasic and reversible processes, and the effects of urea and GdnHCl on PTPase were similar to that of mixed-type reversible inhibitors. Far-ultraviolet (UV) circular dichroism (CD), Tryptophan and 1-anilinonaphthalene -8-sulfonic acid (ANS) fluorescence spectral analyses indicated the existence of a partially active and an inactive molten globule-like intermediate during the unfolding processes induced by urea and GdnHCl, respectively. Based on the sequence alignment and the homolog Tt1001 protein structure, we discussed the possible conformational transitions of PTPase induced by urea and GdnHCl and compared the conformations of these unfolding intermediates with the transient states in bovine PTPase and its complex structures in detail. Our results may be able to provide some valuable clues to reveal the relationship between the structure and enzymatic activity, and the unfolding pathway and mechanism of PTPase.

[Role of Toll-like receptor 2/4-nuclear factor-κB signaling pathway in invasion of Mycobacterium tuberculosis to mouse dendritic cells].

OBJECTIVE: To investigate the mechanism of Mycobacterium tuberculosis invasion to mouse dendritic cells (DC). METHODS: Mycobacterium tuberculosis strain H37Rv was co-cultured with mouse DC2.4 cells.The mRNA expression of Toll-like receptor 2/4(TLR2/4) in DC2.4 cells was detected by fluorescent quantitative real-time PCR and the protein expression of nuclear factor κB(NF-κB) was assessed by Western blotting.The extracellular concentration of tumor necrosis factor α(TNF-α) was measured by ELISA methods during Mycobacterium Tuberculosis invasion.Indirect immunofluorescent staining and flow cytometry assay were used to detect the expression of CD80 and CD86 on DC2.4 cells before and after invasion. RESULTS: The invasion of Mycobacterium tuberculosis in DC2.4 cells was observed after 2 h of co-incubation.The rates of invasion were (37.9±5.6)%,(51.2±7.6)%,(57.2±8.9)% and(63.9±6.8)% at 6,8,10 and 12 h after co-incubation,respectively.The mRNA expression level of TLR2 /4 was significantly increased at 6 h but decreased at 10 h after co-incubation.The expressions of NF-κB p65 and TNF-α were higher in DC2.4 cells after being invaded by 6,8,and 10 h and then gradually decreased.CD80 and CD86 expression were increased on DC2.4 at 6 h after co-incubation. CONCLUSION: Invasion of Mycobacterium tuberculosis strain H37Rv to DC might enhance its antigen-presenting function through activation of TLR2/4-NF-kB signaling pathway.

[Risk factors related to mental disorder in patients with craniocerebral injury].

OBJECTIVE: To explore the correlation between mental disorder and craniocerebral injury, and notifying its related risk factors. METHODS: 342 patients from Sep. 2008 to Sep. 2012 with craniocerebral injury were selected and related clinical data on general their conditions, including sex, age, educational level, satisfaction on careers and relations to family were collected. All the patients received CT-scans to the head, IQ test, MQ test, SCID-1/P, PDQC and SCICP detection. Multivariate logistic regression was used to analyze the general information and cerebral injurious conditions of patients regarding the incidence of mental disorders. RESULTS: 249 patients with mental disorder were noticed out of the total 342 patients with craniocerebral injury, with the incidence rate as 72.8% including 117 depression (47.0%), 95 anxiety disorders (38.2%), 27 mania (10.8%), 69 intelligence and memory disorders (27.7%) cases. Data from correlation analysis showed that factors as sex, age, educational level, satisfaction on careers and family of patients as well as type, severity and location of the craniocerebral injuries appeared to have important correlation with mental disorder. RESULTS: also showed that the age of patients (OR > 1.04), severity and location of the craniocerebral injuries (OR1 > 1.28, OR2 > 1.31) were independent risk factors (P < 0.05). CONCLUSION: The age of patients, severity and location of the craniocerebral injuries were independent risk factors for mental disorder in patients with craniocerebral injury.

[Expression of vascular growth factors in intestinal tissues in colorectal carcinoma patients with schistosomiasis japonica].

OBJECTIVE: To investigate the differences of mRNA quantitation and protein expression of vascular growth factors including platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) in intestinal tissues in colorectal carcinoma patients with and without schistosomiasis. METHODS: Thirty colorectal carcinoma patients with schistosomiasis and 30 colorectal carcinoma patients without schistosomiasis were included in this study. The mRNA quantitation and protein expression of PD-ECGF and VEGF in the normal tissue, peri-carcinoma tissue as well as carcinoma tissue obtained from surgical specimens were detected by qRT-PCR and Western blot. RESULTS: The mRNA relative quantitations of PD-ECGF in normal tissue, peri-carcinoma tissue and carcinoma tissue in the colorectal carcinoma patients with schistosomiasis were 1.726, 1.766 and 2.729 times to those in the colorectal carcinoma patients without schistosomiasis, respectively. The corresponding ones of VEGF were 2.138, 1.831 and 3.376 times, respectively. The protein expression levels of PD-ECGF and VEGF in normal tissue, peri-carcinoma tissue and carcinoma tissue were higher in the colorectal carcinoma patients with schistosomiasis than in the colorectal carcinoma patients without schistosomiasis. CONCLUSIONS: The expressions of vascular growth factors including PD-ECGF and VEGF are higher in the colorectal carcinoma patients with schistosomiasis than in the colorectal carcinoma patients without schistosomiasis. Therefore, schistosomiasis may be one of the risk factors of colorectal cancer.

Localization of Vibrio vulnificus infection in dendritic cells and its effects on the cytoskeleton.

BACKGROUND: Vibrio vulnificus (Vv) is an estuarine bacterium that can cause primary septicemia as well as serious wound infections. However, little is known about the mechanisms by which Vv infects dendritic cells (DCs) and its effects on cytoskeleton. In this study, we aimed to investigate the invasion, internalization, and the organelles damage of the cultured dendritic cells (a DC 2.4 strain) during Vv infection. METHODS: The study model was the cultured DCs infected by a Vv 1.758 strain. Electron microscopy was used to observe the localization of bacteria at the different time points of infection, cell morphology, and the process of organelles changes. The cytoskeleton structure including the microfilaments and the microtubules rearrangement was examined under a fluorescence microscope. RESULTS: The Vv were pinocytosised into the DC cells through double-sides, and localized at 1 - 2 mm of the inner side membrane. It took 1.3, 1.9, and 3.4 hours to reach the infection ratio of 25%, 50%, and 75%, respectively. Using electron microscopy, the DCs had been observed to have developed chromatin aggregation within 4.0 hours, and significant cytoskeleton structure disruption was noted within 6.0 hours. CONCLUSION: The high lethality of Vv infection may be associated with the direct disruption of the DCs cytoskeleton structure.