Publications by authors named "Xin Xu"

2,797 Publications

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A voice recognition-based digital cognitive screener for dementia detection in the community: Development and validation study.

Front Psychiatry 2022 22;13:899729. Epub 2022 Jul 22.

School of Public Health and The Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China.

Introduction: To facilitate community-based dementia screening, we developed a voice recognition-based digital cognitive screener (digital cognitive screener, DCS). This proof-of-concept study aimed to investigate the reliability, validity as well as the feasibility of the DCS among community-dwelling older adults in China.

Methods: Eligible participants completed demographic, clinical, and the DCS. Diagnosis of mild cognitive impairment (MCI) and dementia was made based on the Montreal Cognitive Assessment (MoCA) (MCI: MoCA < 23, dementia: MoCA < 14). Time and venue for test administration were recorded and reported. Internal consistency, test-retest reliability and inter-rater reliability were examined. Receiver operating characteristic (ROC) analyses were conducted to examine the discriminate validity of the DCS in detecting MCI and dementia.

Results: A total of 103 participants completed all investigations and were included in the analysis. Administration time of the DCS was between 5.1-7.3 min. No significant difference ( > 0.05) in test scores or administration time was found between 2 assessment settings (polyclinic or community center). The DCS showed good internal consistency (Cronbach's alpha = 0.73), test-retest reliability (Pearson = 0.69, < 0.001) and inter-rater reliability (ICC = 0.84). Area under the curves (AUCs) of the DCS were 0.95 (0.90, 0.99) and 0.77 (0.67, 086) for dementia and MCI detection, respectively. At the optimal cut-off (7/8), the DCS showed excellent sensitivity (100%) and good specificity (80%) for dementia detection.

Conclusion: The DCS is a feasible, reliable and valid digital dementia screening tool for older adults. The applicability of the DCS in a larger-scale community-based screening stratified by age and education levels warrants further investigation.
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http://dx.doi.org/10.3389/fpsyt.2022.899729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354045PMC
July 2022

Beclin1 Deficiency Suppresses Epileptic Seizures.

Front Mol Neurosci 2022 22;15:807671. Epub 2022 Jul 22.

Chongqing Key Laboratory of Neurology, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Epilepsy is a common disease of the nervous system. Autophagy is a degradation process involved in epilepsy, and in turn, seizures can activate autophagy. Beclin1 plays a critical role in autophagy and participates in numerous physiological and pathological processes. However, the mechanism underlying the effect of Beclin1 on epilepsy remains unclear. In this study, we detected increased expression of Beclin1 in brain tissues from patients with temporal lobe epilepsy (TLE). Heterozygous disruption of decreased susceptibility to epilepsy and suppressed seizure activity in two mouse epilepsy models. We further illustrated for the first time that heterozygous disruption of suppresses excitatory synaptic transmission, which may be caused by a decreased dendritic spine density. These findings suggest for the first time that the regulation of Beclin1 may serve as a strategy for antiepileptic therapy. In addition, Beclin1 participates in synaptic transmission, and the development of dendritic spines may be a biological function of Beclin1 independent of its role in autophagy.
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http://dx.doi.org/10.3389/fnmol.2022.807671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354790PMC
July 2022

N-mytistoyltransferase 1 and 2 are potential tumor suppressors and novel targets of miR-182 in human non-small cell lung carcinomas.

Lung Cancer 2022 Jul 29;171:70-81. Epub 2022 Jul 29.

Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China. Electronic address:

Background & Aims: Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancer diagnoses across the world. Despite recent appreciable improvements in treatment plans for patients with NSCLC, the prognosis for those with the cancer still remains poor. Recently, a growing number of studies have shown that N-myristoyltransferases (NMTs) may be critical in carcinogenesis, however, the functional and clinical significance of this pathway in NSCLC remains unclear and requires further research.

Methods: Initially, we evaluated the expression levels of NMT1 or NMT2 in a clinical cohort comprising of 303 paired primary NSCLC tissues and matched normal mucosae by using ELISA. We subsequently performed a tissue microarray analysis (TMA) to confirm its expression pattern in an independent validation cohort (n = 78). Then, we used a publicly available KM plotter database (n = 1921) to evaluate the prognostic impact of NMT1 and NMT2 in NSCLC. Lastly, a series of in-vitro molecular/cellular and animal experiments were performed for mechanistic understanding of the role of N-myristoyltransferases in NSCLC.

Results: Our ELISA data revealed that the expression level of NMT1 and NMT2 was down-regulated in tumor tissues (n = 303, P < 0.0001), which was confirmed in an independent validation cohort by TMA (n = 78, P = 0.014 for NMT1 and P < 0.0001 for NMT2). On the other hand, patients with low expression of NMT1 or NMT2 had shorter overall survival (P = 0.013, HR = 0.85 for NMT1; P = 0.00059, HR = 0.8, for NMT2). Mechanistically, we revealed that the interaction and co-localization of NMT1 and NMT2 in NSCLC, and N-terminus of NMT1 and NMT2 was observed to be crucial for their interaction as well as for their catalytic activity. Moreover, we found that NMT1 can significantly promote the expression of NMT2 by enhancing its stability. We corroborated these findings by performing functional assays in which the knockout of NMT1 and NMT2 resulted in enhanced cell proliferation, migration and invasion as well as increased tumorxenograftgrowth. In addition, we identified miR-182 as a novel regulator of both NMT1 and NMT2. More specifically, the overexpression or inhibition of miR-182 modulated globe N-myristoylation level, contributed to phenotypic alterations in NSCLS cells.

Conclusions: NMT1 and NMT2 can act as potential tumor suppressors in NSCLC, and the inhibition of miR-182 expression or therapeutic NMTs replenishment may be a promising treatment option for patients with NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2022.07.021DOI Listing
July 2022

Catastrophic health expenditure among Chinese adults living alone with cognitive impairment: findings from the CHARLS.

BMC Geriatr 2022 08 4;22(1):640. Epub 2022 Aug 4.

Department of Big Data in Health Science School of Public Health and Center for Clinical Big Data and Analytics of the Second Affiliated Hospital, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Zhejiang, 310058, Hangzhou, China.

Background: The catastrophic health expenditure of older adults results in serious consequences; however, the issue of whether cognitive status and living situations contribute to such financial burdens is uncertain. Our aim was to compare the differences in catastrophic health expenditure between adults living alone with cognitive impairment and those adults living with others and with normal cognition.

Methods: We identified 909 observations of participants living alone with cognitive impairment (cases) and 37,432 observations of participants living with others and with normal cognition (comparators) from the 2011/2012, 2013, 2015 and 2018 waves of the China Health and Retirement Longitudinal Study (CHARLS). We used propensity score matching (1:2) to create matched cases and comparators in a covariate-adjusted logistic regression analysis. Catastrophic health expenditure was defined as an out-of-pocket cost for health care ≥40% of a household's capacity to pay.

Results: In comparison with participants living with others and with normal cognition, those adults living alone with cognitive impairment reported a higher percentage of catastrophic health expenditure (19.5% vs. 11.8%, respectively, P < 0.001). When controlling for age, sex, education, marital status, residence areas, alcohol consumption, smoking status and disease counts, we found that this subpopulation had significantly higher odds of having catastrophic health expenditure (odds ratio [OR] = 1.89, 95% confidence interval [CI]: 1.40, 2.56). Additional analyses confirmed the robustness of the results.

Conclusions: This study demonstrated that adults living alone with cognitive impairment in the CHARLS experienced a high burden of catastrophic health expenditure. Health care policies on social health insurance and medical assistance should consider these vulnerable adults.
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http://dx.doi.org/10.1186/s12877-022-03341-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351200PMC
August 2022

The protective effect of DNA aptamer on osteonecrosis of the femoral head by alleviating TNF-α-mediated necroptosis via RIP1/RIP3/MLKL pathway.

J Orthop Translat 2022 Sep 21;36:44-51. Epub 2022 Jul 21.

Peking University Health Science Center, China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China.

Background: The process of necroptosis mediated by tumor necrosis factor alpha (TNF-α) might play an important role in the onset and development of the osteonecrosis of the femoral head (ONFH). The dysfunctions of bone microvascular endothelial cells (BMECs) have been identified as an important part of pathological processes in the steroid-induced ONFH. An aptamer is a single-stranded DNA or RNA oligonucleotide sequence. Previous studies have designed or screened various aptamers that could bind to specific targets or receptors in order to block their effects.

Objective: There are two main objectives in this study: 1) to establish a TNF-α -induced ONFH model in human BMECs in vitro, 2) to verify the effects of the TNF-α aptamer (AptTNF-α) on blocking TNF-α activity in the ONFH model.

Methods: Clinical samples were collected for Hematoxylin and Eosin (HE) staining, immunohistochemistry and further BMEC isolation. After cell culture and identification, the cell viability of BMECs after incubation with TNF-α was assessed by Cell Counting Kit-8 (CCK8). The necroptosis of BMECs was detected by the TUNEL and Annexin V-FITC/PI staining. The attenuation of TNF-α cytotoxicity by AptTNF-α was evaluated by CCK8 at first. Then, the molecular mechanism was explored by the quantitative real-time polymerase chain reaction and western blotting.

Results: The expression level of TNF-α was significantly up-regulated in bone tissues of ONFH patients. The identification of BMECs was verified by the high expressions of CD31 and vWF. Results from CCK8, TUNEL staining and Annexin V-FITC/PI assay demonstrated reduced cell viability and increased necroptosis of BMECs after TNF-α stimulation. Further investigations showed that TNF-α cytotoxicity could be attenuated by the AptTNF-α in a dose-dependent manner. Necroptosis mediated by TNF-α in the ONFH model was regulated by the receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) signalling pathway.

Conclusion: We established a TNF-α-induced ONFH model in human BMECs in vitro. Our study also demonstrated that the AptTNF-α could protect BMECs from necroptosis by inhibiting the RIP1/RIP3/MLKL signalling pathway.: The effective protection from cell necroptosis provided by the DNA aptamer demonstrated its translational potential as a new type of TNF-α inhibitor in clinical treatments for patients with ONFH.
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http://dx.doi.org/10.1016/j.jot.2022.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307900PMC
September 2022

Associations between dietary fiber intake and mortality from all causes, cardiovascular disease and cancer: a prospective study.

J Transl Med 2022 Aug 2;20(1):344. Epub 2022 Aug 2.

Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Objective: Several studies suggest that dietary fiber intake may reduce mortality risk, but this might depend on the fiber types and the evidence regarding the role of soluble fiber or insoluble fiber on death risk remain limited and inconsistent. Therefore, this study aimed to comprehensively evaluate multiple types of dietary fiber intake on mortality from all causes, cardiovascular disease and cancer in the large-scale Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial.

Methods: A multivariate Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: This study finally included 86,642 participants with 17,536 all-cause deaths, 4842 cardiovascular deaths and 5760 cancer deaths identified after a total of 1,444,068 follow-up years. After adjusting for potential confounders, dietary total fiber intake was statistically significantly inversely associated with all-cause death (Q5 vs Q1: HR 0.71, 95% CI 0.66-0.75; P for trend < 0.001), cardiovascular death (Q5 vs Q1: HR 0.73, 95% CI 0.65-0.83; P for trend < 0.001) and cancer mortality (Q5 vs Q1: HR 0.77, 95% CI 0.69-0.86; P for trend < 0.001). Similar results were observed for both insoluble and soluble fiber intake. Restricted cubic spline model analysis suggested that there was a nonlinear association of dietary fiber intake with mortality risk (all P for nonlinearity < 0.05).

Conclusions: In this large nationally representative sample of US adult population, intakes of total fiber, soluble fiber, and insoluble fiber were associated with lower risks of all-cause, cardiovascular and cancer mortality.
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http://dx.doi.org/10.1186/s12967-022-03558-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344643PMC
August 2022

Unexpected steric hindrance failure in the gas phase F + (CH)CI S2 reaction.

Nat Commun 2022 Jul 30;13(1):4427. Epub 2022 Jul 30.

State Key Laboratory of Molecular Reaction Dynamics and Center for Theoretical and Computational Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, Dalian, 116023, China.

Base-induced elimination (E2) and bimolecular nucleophilic substitution (S2) reactions are of significant importance in physical organic chemistry. The textbook example of the retardation of S2 reactivity by bulky alkyl substitution is widely accepted based on the static analysis of molecular structure and steric environment. However, the direct dynamical evidence of the steric hindrance of S2 from experiment or theory remains rare. Here, we report an unprecedented full-dimensional (39-dimensional) machine learning-based potential energy surface for the 15-atom F + (CH)CI reaction, facilitating the reliable and efficient reaction dynamics simulations that can reproduce well the experimental outcomes and examine associated atomic-molecular level mechanisms. Moreover, we found surprisingly high "intrinsic" reactivity of S2 when the E2 pathway is completely blocked, indicating the reaction that intends to proceed via E2 transits to S2 instead, due to a shared pre-reaction minimum. This finding indicates that the competing factor of E2 but not the steric hindrance determines the small reactivity of S2 for the F + (CH)CI reaction. Our study provides new insight into the dynamical origin that determines the intrinsic reactivity in gas-phase organic chemistry.
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http://dx.doi.org/10.1038/s41467-022-32191-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338938PMC
July 2022

Transposon mutagenesis in oral .

J Oral Microbiol 2022 24;14(1):2104951. Epub 2022 Jul 24.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, China.

Oral streptococci are gram-positive facultative anaerobic bacteria that are normal inhabitants of the human oral cavity and play an important role in maintaining oral microecological balance and pathogenesis. Transposon mutagenesis is an effective genetic manipulation strategy for studying the function of genomic features. In order to study cariogenic related genes and crucial biological element genes of oral Streptococcus, transposon mutagenesis was widely used to identify functional genes. With the advent of next-generation sequencing (NGS) technology and the development of transposon random mutation library construction methods, transposon insertion sequencing (TIS) came into being. Benefiting from high-throughput advances in NGS, TIS was able to evaluate the fitness contribution and essentiality of genetic features in the bacterial genome. The application of transposon mutagenesis, including TIS, to oral streptococci provided a massive amount of valuable detailed linkage data between genetic fitness and genetic backgrounds, further clarify the processes of colonization, virulence, and persistence and provides a more reliable basis for investigating relationships with host ecology and disease status. This review focuses on transposon mutagenesis, including TIS, and its applicability in oral streptococci.
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http://dx.doi.org/10.1080/20002297.2022.2104951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318214PMC
July 2022

Expanding local sales restrictions on flavoured tobacco products to include menthol: retail sales changes in two Minnesota cities.

Tob Control 2022 Jul 28. Epub 2022 Jul 28.

Clearway Minnesota, Minneapolis, Minnesota, USA.

Background: In 2018, Minneapolis and St. Paul, Minnesota, expanded existing local sales restrictions on flavoured (non-menthol/mint/wintergreen) tobacco products ('flavour policies') to include menthol/mint/wintergreen-flavoured tobacco products ('menthol policies'). All policies included exemptions for certain store types.

Methods: We obtained weekly retail tobacco product sales for 2015 through 2019 from NielsenIQ for convenience stores and other outlets in the policy jurisdictions and two comparison areas (rest of the state of Minnesota and total USA). We standardised unit sales across product categories and used NielsenIQ-provided descriptors to classify products as menthol (including mint/wintergreen) or flavoured (non-menthol/non-tobacco). Using single group interrupted time series models, we analysed unit sales by product category and by flavour separately for each geography to assess associations between menthol policy implementation and trends in tobacco product unit sales.

Results: Following menthol policy implementation, unit sales of menthol cigarettes and menthol smokeless tobacco decreased in both cities, with smaller decreases in comparison areas. Flavoured cigar sales-which decreased following the flavour policies-further decreased after the menthol policies, while sales of menthol electronic nicotine delivery systems (ENDS) increased in both cities and sales of flavoured ENDS increased in St. Paul.

Conclusion: Expanding flavour policies to include menthol/mint/wintergreen was associated with significant decreases in unit sales of most menthol products and in total unit sales by tobacco product category. Increases in menthol and flavoured ENDS sales in these cities may be associated with legal sales by exempted retailers and/or illicit sales by non-compliant retailers, highlighting opportunities for retailer education and enforcement.
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http://dx.doi.org/10.1136/tc-2022-057392DOI Listing
July 2022

Effects of Laser Machining Aluminum Alloy in Different Media.

Micromachines (Basel) 2022 Jul 17;13(7). Epub 2022 Jul 17.

School of Mechanical and Electrical Engineering, Anhui Jianzhu University, No. 292, Ziyun Road, Hefei 230601, China.

To study the effects of aluminum alloys processed by a laser in air and water and at different water velocities, corresponding experiments were conducted and the impacting effects of different water velocities on the surface of the workpiece were simulated, respectively. The results show that when laser processing aluminum alloy materials in air, there is more slag and a recondensation layer on both sides of the groove, the heat-affected zone is larger and the surface processing quality is poor. When laser processing aluminum alloy materials in water, the processing quality is improved. With the increase in water velocity, the impacting and cooling effect is enhanced, the groove depth and groove width show a trend of first increasing and then decreasing, the slag and recondensation layer on both sides of the groove are reduced, the heat-affected zone is reduced and the processing quality of the groove is improved. When the water velocity reaches 30 m/s, a better groove can be obtained. Laser processing aluminum alloy materials in water can obtain better processing quality than laser processing in air.
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http://dx.doi.org/10.3390/mi13071130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323413PMC
July 2022

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons in Firefighters: A Systematic Review and Meta-Analysis.

Int J Environ Res Public Health 2022 Jul 11;19(14). Epub 2022 Jul 11.

Shanghai Anti-Doping Laboratory, Shanghai University of Sport, Shanghai 200438, China.

Firefighters are intermittently exposed to complex, mixed pollutants in random settings. Of those pollutants, PAHs (polycyclic aromatic hydrocarbons) are the most commonly studied and best understood. PAH exposure can occur via multiple routes; therefore, the levels of hydroxylated metabolites of PAHs in urine have been used as a biomonitoring tool for risk assessment. We performed a systematic review and meta-analysis of the literature to estimate the levels of urinary hydroxylated PAH (OHPAH) among firefighters, determine risk attributions, and, finally, evaluate the scope of preventive efforts and their utility as diagnostic tools. The meta-regression confirmed increases in OHPAH concentrations after fire activities by up to 1.71-times (-values: <0.0001). Samples collected at a time point of 2-4 h after a fire suppression showed a consistent, statistically significant pattern as compared with baseline samples. The National Fire Protection Association (NFPA) standard 1582 lists various health examinations, including a urinalysis for occupational chemical exposure if indicated and medical screening for cancers and cardiovascular diseases. Biomonitoring is a valuable screening tool for assessing occupational exposure and the results of this meta-analysis support their inclusion in regular health screenings for firefighters.
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http://dx.doi.org/10.3390/ijerph19148475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318785PMC
July 2022

Pancreatic necrosis volume for predicting readmission and reintervention in acute necrotizing pancreatitis.

Eur J Radiol 2022 Jun 22;154:110419. Epub 2022 Jun 22.

Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China. Electronic address:

Purpose: To determine the correlation between the pancreatic necrosis volume (PNV) and readmission as well as reintervention.

Method: This was a retrospective cohort study that included necrotizing pancreatitis (NP) patients who were examined with contrast-enhanced computed tomography (CT) one week before discharge. The PNV was calculated manually based on the postprocessing workstation software. Multivariate logistic regression analysis was employed to determine the independent risk factors for readmission and reintervention.

Results: A total of 167 NP patients were included. Among them, 94 (56.3%) patients were readmitted after discharge, and 55 (32.9%) patients needed further invasive intervention. The median PNV of all patients was 376.6 (interquartile range (IQR), 129.3-820.5) cm, and the PNV was significantly higher in patients needing readmission or reintervention. Multivariate analysis showed that PNV ≥ 620 cm (adjusted odds ratio (adjOR), 3.08; 95% confidence interval (CI), 1.47-6.43; P = 0.003) and modified computed tomography severity index (CTSI) score ≥ 7 points (adjOR, 6.36; 95% CI, 2.05-10.70; P = 0.001) were independently associated with readmission. Stent or drainage tube placement at discharge (adjOR, 2.94; 95% CI, 1.27-6.77; P = 0.011), PNV ≥ 620 cm (adjOR, 5.11; 95% CI, 2.19-11.95; P < 0.001), pancreatic parenchymal necrosis (adjOR, 3.37; 95% CI, 1.42-7.96; P = 0.006), and modified CTSI score ≥ 7 points (adjOR, 4.23; 95% CI, 1.46-12.27; P = 0.008) were independent risk factors for reintervention.

Conclusions: The PNV is a useful tool for quantifying pancreatic necrosis and is strongly associated with readmission and reintervention. Additional prospective studies with larger sample sizes are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.ejrad.2022.110419DOI Listing
June 2022

[Latest Research Findings on the Mechanism of Periodontal Pathogens in Cardiovascular Disease].

Sichuan Da Xue Xue Bao Yi Xue Ban 2022 Jul;53(4):732-736

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Dental and Endodontic Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Cardiovascular disease (CVD) is a major cause of death worldwide. Research findings indicate that periodontal infection is an independent risk factor for CVD. Periodontal pathogens can cause cardiovascular diseases through various pathways, including direct invasion, induction of platelet activation and agglutination, immune inflammatory response, bacteremia, and oxidative stress. Moreover, CVD symptoms are relieved after the patients undergo periodontal interventional treatment. There have been substantial findings indicating that there may be a close connection between periodontal disease and CVD. However, periodontal disease is a chronic disease. The treatment of periodontal diseases and the improvement of periodontal health require long-term efforts. Long-term effective reduction of the incidence of CVD in clinical practice through prevention of periodontal disease remains a challenging area of study. Here we summarized and reported the latest findings on the mechanism of action of periodontal pathogens in cardiovascular diseases, intending to contribute to the better understanding of the pathogenesis of CVD and to provide potential targets and new ideas for its prevention and treatment.
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http://dx.doi.org/10.12182/20220760108DOI Listing
July 2022

Association Between Proton Pump Inhibitor Therapy and Spontaneous Bacterial Peritonitis Occurrence in Cirrhotic Patients: A Clinical Review.

Curr Med Sci 2022 Jul 23. Epub 2022 Jul 23.

Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, China.

Spontaneous bacterial peritonitis (SBP) is one of the most common complications in patients with end-stage liver disease (ESLD), which increases the risk of short-term mortality. Proton pump inhibitors (PPIs) are frequently used in patients with ESLD, in which controversies about the risk of PPI treatment in the occurrence of SBP are largely raised and the pathogenic mechanism of PPI-associated SBP remains unclear. We conducted a systematic literature search through PubMed/MEDLINE for publications mainly from 1 January 2000 to 1 January 2021. Our narrative review summarized the adverse effect of specific PPI therapy on the occurrence and prognosis of SBP in cirrhotic patients, described the potential mechanisms by which PPI induces the development of SBP, and discussed the risk factors associated with the development of SBP and the strategy of PPI therapy in cirrhotic patients. Although controversy regarding the association between PPI use and the occurrence of SBP exists, PPIs use should be restricted to patients with clear benefit indications, and be cautious for elderly patients with severe liver damage.
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http://dx.doi.org/10.1007/s11596-022-2607-3DOI Listing
July 2022

Strong non-Arrhenius behavior at low temperatures in the OH + HCl → HO + Cl reaction due to resonance induced quantum tunneling.

Chem Sci 2022 Jul 13;13(26):7955-7961. Epub 2022 Jun 13.

State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian 116023 Liaoning China

The OH + HCl → HO + Cl reaction releases Cl atoms, which can catalyze the ozone destruction reaction in the stratosphere. The measured rate coefficients for the reaction deviate substantially from the Arrhenius limit at low temperatures and become essentially independent of temperature when < 250 K, apparently due to quantum tunneling; however, the nature of the quantum tunneling is unknown. Here, we report a time-dependent wave packet study of the reactions on two newly constructed potential energy surfaces. It is found that the OH + HCl reaction possesses many Feshbach resonances trapped in a bending/torsion excited vibrational adiabatic potential well in the entrance channel due to hydrogen bond interaction. These resonance states greatly induce quantum tunneling of a hydrogen atom through the reaction barrier, causing the reaction rates to deviate substantially from Arrhenius behavior at low temperature, as observed experimentally.
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http://dx.doi.org/10.1039/d2sc01958bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258319PMC
July 2022

Plasma Lipid Mediators Associate With Clinical Outcome After Successful Endovascular Thrombectomy in Patients With Acute Ischemic Stroke.

Front Immunol 2022 4;13:917974. Epub 2022 Jul 4.

Department of Neurosurgery, Liaocheng People's hospital, Liaocheng, China.

Background: Neuroinflammatory response contributes to early neurological deterioration (END) and unfavorable long-term functional outcome in patients with acute ischemic stroke (AIS) who recanalized successfully by endovascular thrombectomy (EVT), but there are no reliable biomarkers for their accurate prediction. Here, we sought to determine the temporal plasma profiles of the bioactive lipid mediators lipoxin A4 (LXA4), resolvin D1 (RvD1), and leukotriene B4 (LTB4) for their associations with clinical outcome.

Methods: We quantified levels of LXA4, RvD1, and LTB4 in blood samples retrospectively and longitudinally collected from consecutive AIS patients who underwent complete angiographic recanalization by EVT at admission (pre-EVT) and 24 hrs post-EVT. The primary outcome was unfavorable long-term functional outcome, defined as a 90-day modified Rankin Scale score of 3-6. Secondary outcome was END, defined as an increase in National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 24 hrs post-EVT.

Results: Eighty-one consecutive AIS patients and 20 healthy subjects were recruited for this study. Plasma levels of LXA4, RvD1, and LTB4 were significantly increased in post-EVT samples from AIS patients, as compared to those of healthy controls. END occurred in 17 (20.99%) patients, and 38 (46.91%) had unfavorable 90-day functional outcome. Multiple logistic regression analyses demonstrated that post-EVT levels of LXA4 (adjusted odd ratio [OR] 0.992, 95% confidence interval [CI] 0.987-0.998), ΔLXA4 (adjusted OR 0.995, 95% CI 0.991-0.999), LTB4 (adjusted OR 1.003, 95% CI 1.001-1.005), ΔLTB4 (adjusted OR 1.004, 95% CI 1.002-1.006), and post-EVT LXA4/LTB4 (adjusted OR 0.023, 95% CI 0.001-0.433) and RvD1/LTB4 (adjusted OR 0.196, 95% CI 0.057-0.682) ratios independently predicted END, and post-EVT LXA4 levels (adjusted OR 0.995, 95% CI 0.992-0.999), ΔLXA4 levels (adjusted OR 0.996, 95% CI 0.993-0.999), and post-EVT LXA4/LTB4 ratio (adjusted OR 0.285, 95% CI 0.096-0.845) independently predicted unfavorable 90-day functional outcome. These were validated using receiver operating characteristic curve analyses.

Conclusions: Plasma lipid mediators measured 24 hrs post-EVT were independent predictors for early and long-term outcomes. Further studies are needed to determine their causal-effect relationship, and whether the imbalance between anti-inflammatory/pro-resolving and pro-inflammatory lipid mediators could be a potential adjunct therapeutic target.
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http://dx.doi.org/10.3389/fimmu.2022.917974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295711PMC
July 2022

gC1qR/C1qBP/HABP-1: Structural Analysis of the Trimeric Core Region, Interactions With a Novel Panel of Monoclonal Antibodies, and Their Influence on Binding to FXII.

Front Immunol 2022 5;13:887742. Epub 2022 Jul 5.

Department of Biochemistry & Molecular Biophysics, Kansas State University, Manhattan, KS, United States.

The protein gC1qR/C1qBP/HABP-1 plays an essential role in mitochondrial biogenesis, but becomes localized at the cellular surface in numerous pathophysiological states. When this occurs on endothelial cells, surface-exposed gC1qR activates the classical pathway of complement. It also promotes assembly of a multi-protein complex comprised of coagulation factor XII (FXII), pre-kallikrein (PK), and high-molecular weight kininogen (HMWK) that activates the contact system and the kinin-generating system. Since surface-exposed gC1qR triggers intravascular inflammatory pathways, there is interest in identifying molecules that block gC1qR function. Here we further that objective by reporting the outcome of a structure/function investigation of gC1qR, its interactions with FXII, and the impact of a panel of monoclonal anti-gC1qR antibodies on FXII binding to gC1qR. Although deletion mutants have been used extensively to assess gC1qR function, none of these proteins have been characterized structurally. To that end, we determined a 2.2 Å resolution crystal structure of a gC1qR mutant lacking both of its acidic loops, but which retained nanomolar-affinity binding to FXII and FXIIa. This structure revealed that the trimeric gC1qR assembly was maintained despite loss of roughly thirty residues. Characterization of a novel panel of anti-gC1qR monoclonal antibodies identified several with biochemical properties distinct from previously described antibodies, as well as one which bound to the first acidic loop of gC1qR. Intriguingly, we found that each of these antibodies could partly inhibit binding of FXII and FXIIa to gC1qR. Based on these results and previously published studies, we offer new perspectives for developing gC1qR inhibitors.
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http://dx.doi.org/10.3389/fimmu.2022.887742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294231PMC
July 2022

PTHrP promotes subchondral bone formation in TMJ-OA.

Int J Oral Sci 2022 Jul 19;14(1):37. Epub 2022 Jul 19.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.

PTH-related peptide (PTHrP) improves the bone marrow micro-environment to activate the bone-remodelling, but the coordinated regulation of PTHrP and transforming growth factor-β (TGFβ) signalling in TMJ-OA remains incompletely understood. We used disordered occlusion to establish model animals that recapitulate the ordinary clinical aetiology of TMJ-OA. Immunohistochemical and histological analyses revealed condylar fibrocartilage degeneration in model animals following disordered occlusion. TMJ-OA model animals administered intermittent PTHrP (iPTH) exhibited significantly decreased condylar cartilage degeneration. Micro-CT, histomorphometry, and Western Blot analyses disclosed that iPTH promoted subchondral bone formation in the TMJ-OA model animals. In addition, iPTH increased the number of osterix (OSX)-positive cells and osteocalcin (OCN)-positive cells in the subchondral bone marrow cavity. However, the number of osteoclasts was also increased by iPTH, indicating that subchondral bone volume increase was mainly due to the iPTH-mediated increase in the bone-formation ability of condylar subchondral bone. In vitro, PTHrP treatment increased condylar subchondral bone marrow-derived mesenchymal stem cell (SMSC) osteoblastic differentiation potential and upregulated the gene and protein expression of key regulators of osteogenesis. Furthermore, we found that PTHrP-PTH1R signalling inhibits TGFβ signalling during osteoblastic differentiation. Collectively, these data suggested that iPTH improves OA lesions by enhancing osteoblastic differentiation in subchondral bone and suppressing aberrant active TGFβ signalling. These findings indicated that PTHrP, which targets the TGFβ signalling pathway, may be an effective biological reagent to prevent and treat TMJ-OA in the clinic.
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http://dx.doi.org/10.1038/s41368-022-00189-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296483PMC
July 2022

Identification of Selective CYP3A7 and CYP3A4 Substrates and Inhibitors Using a High-Throughput Screening Platform.

Front Pharmacol 2022 1;13:899536. Epub 2022 Jul 1.

Division of Pre-Clinical Innovation, National Center for Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, United States.

Cytochrome P450 (CYP) 3A7 is one of the major xenobiotic metabolizing enzymes in human embryonic, fetal, and newborn liver. CYP3A7 expression has also been observed in a subset of the adult population, including pregnant women, as well as in various cancer patients. The characterization of CYP3A7 is not as extensive as other CYPs, and health authorities have yet to provide guidance towards DDI assessment. To identify potential CYP3A7-specific molecules, we used a P450-Glo CYP3A7 enzyme assay to screen a library of ∼5,000 compounds, including FDA-approved drugs and drug-like molecules, and compared these screening data with that from a P450-Glo CYP3A4 assay. Additionally, a subset of 1,000 randomly selected compounds were tested in a metabolic stability assay. By combining the data from the qHTS P450-Glo and metabolic stability assays, we identified several chemical features important for CYP3A7 selectivity. Halometasone was chosen for further evaluation as a potential CYP3A7-selective inhibitor using molecular docking. From the metabolic stability assay, we identified twenty-two CYP3A7-selective substrates over CYP3A4 in supersome setting. Our data shows that CYP3A7 has ligand promiscuity, much like CYP3A4. Furthermore, we have established a large, high-quality dataset that can be used in predictive modeling for future drug metabolism and interaction studies.
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http://dx.doi.org/10.3389/fphar.2022.899536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283723PMC
July 2022

The Evaluation of a SEER-Based Nomogram in Predicting the Survival of Patients Treated with Neoadjuvant Therapy Followed by Esophagectomy.

Front Surg 2022 29;9:853093. Epub 2022 Jun 29.

Department of Thoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.

Background: A novel nomogram based on the Surveillance, Epidemiology, and End Results (SEER) database has been developed to predict the survival of patients with esophageal carcinoma who received neoadjuvant therapy followed by surgery. We aimed to evaluate the accuracy and value of the nomogram with an external validation cohort.

Methods: A total of 2,224 patients in SEER database were divided into the training cohort ( = 1556) and the internal validation cohort ( = 668), while 77 patients in our institute were enrolled in the external validation cohort. A Cox proportional hazards regression model was used to develop a nomogram based on the training cohort, while the C-indexes, the calibration curves, receiver operating characteristics curve (ROC), and Kaplan-Meier survival curve were applied in the internal and external validation cohort.

Results: Five independent risk factors were identified and integrated into the nomogram (C-index = 0.645, 95%CI 0.627-0.663). The nomogram exhibited good prognostic value in the internal validation cohort (C-index = 0.648 95%CI 0.622-0.674). However, the C-index, calibration plot, receiver operating characteristics curve (ROC) analysis, Kaplan-Meier survival curve of the nomogram in the external validation cohort were not as good as the training and internal validation cohort (C-index = 0.584 95%CI 0.445-0.723). Further analysis demonstrated that the resection margin involvement (R0, R1, or R2 resection) was an independent risk factor for the patients, which was not included in the SEER cohort.

Conclusions: the nomogram based on the SEER database fails to accurately predict the prognosis of the patients in the external validation cohort, which can be caused by the absence of essential information from the SEER database.
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http://dx.doi.org/10.3389/fsurg.2022.853093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276989PMC
June 2022

Association of Maternal Mild Hypothyroidism With Offspring Neurodevelopment in TPOAb-Negative Women: A Prospective Cohort Study.

Front Endocrinol (Lausanne) 2022 29;13:884851. Epub 2022 Jun 29.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Objectives: Adequate maternal thyroid hormone availability is crucial for fetal neurodevelopment, but the role of maternal mild hypothyroidism is not clear. We aim to investigate the association of maternal mild hypothyroidism with neurodevelopment in infants at 1 year of age among TPOAb-negative women.

Methods: The present study was conducted within the Jiangsu Birth Cohort. A total of 793 mother-infant pairs were eligible for the present study. Maternal thyroid function was assessed by measuring serum thyroid-stimulating hormone, free thyroxine, and thyroid peroxidase antibodies. Neurodevelopment of infants was assessed by using the Bayley Scales of Infant and Toddler Development third edition screening test (Bayley-III screening test).

Results: In the multivariate adjusted linear regression analyses, infants of women with subclinical hypothyroidism and isolated hypothyroxinemia were associated with decreased receptive communication scores ( = -0.68, = 0.034) and decreased gross motor scores ( = -0.83, = 0.008), respectively. Moreover, infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L) and low FT4 concentrations were significantly associated with lower gross motor scores ( = -1.19, = 0.032), while no differences were observed in infants when the mothers had a high-normal TSH concentration and normal FT4 levels.

Conclusions: Maternal subclinical hypothyroidism is associated with decreased receptive communication scores in infants at 1 year of age. In addition, maternal TSH concentration greater than 4.0 mIU/L and maternal isolated hypothyroxinemia are associated with impaired gross motor ability of infants, especially in infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L).
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http://dx.doi.org/10.3389/fendo.2022.884851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278520PMC
June 2022

Analysis of Fertility Preservation by Ovarian Tissue Cryopreservation in Pediatric Children in China.

Front Endocrinol (Lausanne) 2022 29;13:930786. Epub 2022 Jun 29.

Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.

Background: Ovarian tissue cryopreservation (OTC) is the only method of fertility preservation (FP) in prepubertal girls, but the experience remains limited. This study investigates the effectiveness and feasibility of FP of OTC in children facing gonadotoxicity treatment in Chinese first ovarian tissue cryobank.

Procedure: OTC and evaluation of 49 children ≤14 years old in the cryobank of Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from July 2017 to May 19, 2022, were analyzed retrospectively. We compared children's general characteristics, follicle numbers, and hormone levels with and without chemotherapy before OTC.

Results: The age of 49 children at the time of OTC was 7.55 (1-14) years old. There were 23 cases of hematological non-malignant diseases, eight cases of hematological malignant diseases, four cases of gynecological malignant tumors, one case of neurological malignant tumors, one case of bladder cancer, five cases of sarcoma, three cases of mucopolysaccharidosis, one case of metachromatic leukodystrophy, two cases of dermatomyositis, one case of Turner's syndrome. The median follicular count per 2-mm biopsy was 705. Age and AMH were not correlated (r = 0.084, 0.585). Age and follicle count per 2-mm biopsy was not correlated (r = -0.128, 0.403). Log10 (follicle count per 2-mm biopsy) and Log10 (AMH) were not correlated (r = -0.118, 0.456). Chemotherapy before OTC decreased AMH levels but had no significant effect on the number of follicles per 2-mm biopsy.

Conclusions: OTC is the only method to preserve the fertility of prepubertal girls, and it is safe and effective. Chemotherapy before OTC is not a contraindication to OTC.
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http://dx.doi.org/10.3389/fendo.2022.930786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277002PMC
June 2022

Excimer laser ablation combined with drug-coated balloon versus drug-coated balloon in the treatment of de novo atherosclerotic lesions in lower extremities (ELABORATE): study protocol for a real-world clinical trial.

BMC Cardiovasc Disord 2022 07 16;22(1):317. Epub 2022 Jul 16.

Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Shanghai, 200032, China.

Background: The efficacy and validity of excimer laser ablation (ELA) in the in-stent restenosis (ISR) has been confirmed. However, its application in de novo atherosclerotic lesions of lower extremity artery disease (LEAD) has not been clearly defined and its procedure has not been standardized.

Methods: ELABORATE is a prospective, multicenter, real-world study designed to evaluate the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in de novo atherosclerotic lesions of LEAD.

Discussion: ELABORATE is a prospective, multicenter, real-world study designed to assess the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in patients with de novo atherosclerotic lesions of LEAD. According to the real-world situation, eligible patients will be allocated to ELA + DCB group (group E) and DCB group (group C). Baseline and follow-up information (at 3, 6, and 12 months) will be collected. The primary efficacy point is primary patency at 12-months, and the secondary efficacy points include clinically driven target lesion reintervention (CD-TLR), change of Rutherford class, ankle-brachial index and ulcer healing rate. These indexes will be assessed and recorded at 3, 6, and 12-month follow-up. Also, safety evaluation, including major adverse event, all-cause mortality through 30-day follow-up, unplanned major amputation, bailout stent and distal embolization, will also be evaluated by an independent core laboratory. All the data will be collected and recorded by the electric data capture system. This study will be finished in 3 years and the 12-month results will be available in 2023. All the patients will be followed for 5 years. Trial registration number Chinese Clinical Trial Registry (ChiCTR2100051263). Registered 17 September 2019. http://www.chictr.org.cn/listbycreater.aspx .
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http://dx.doi.org/10.1186/s12872-022-02751-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287897PMC
July 2022

Somatic cell fate maintenance in mouse fetal testes via autocrine/paracrine action of AMH and activin B.

Nat Commun 2022 Jul 15;13(1):4130. Epub 2022 Jul 15.

Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Durham, NC, USA.

Fate determination and maintenance of fetal testes in most mammals occur cell autonomously as a result of the action of key transcription factors in Sertoli cells. However, the cases of freemartin, where an XX twin develops testis structures under the influence of an XY twin, imply that hormonal factor(s) from the XY embryo contribute to sex reversal of the XX twin. Here we show that in mouse XY embryos, Sertoli cell-derived anti-Mullerian hormone (AMH) and activin B together maintain Sertoli cell identity. Sertoli cells in the gonadal poles of XY embryos lacking both AMH and activin B transdifferentiate into their female counterpart granulosa cells, leading to ovotestis formation. The ovotestes remain to adulthood and produce both sperm and oocytes, although there are few of the former and the latter fail to mature. Finally, the ability of XY mice to masculinize ovaries is lost in the absence of these two factors. These results provide insight into fate maintenance of fetal testes through the action of putative freemartin factors.
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http://dx.doi.org/10.1038/s41467-022-31486-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287316PMC
July 2022

Accurate and Efficient Estimation of Lennard-Jones Interactions for Coarse-Grained Particles via a Potential Matching Method.

J Chem Theory Comput 2022 Aug 15;18(8):4879-4890. Epub 2022 Jul 15.

Collaborative Innovation Center of Chemistry for Energy Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, MOE Key Laboratory of Computational Physical Sciences, Departments of Chemistry, Fudan University, Shanghai 200433, China.

The Lennard-Jones (LJ) energy functions are commonly used to describe the nonbonded interactions in bulk coarse-grained (CG) models, which contribute significantly to the stabilization of a local binding configuration or a self-assembly system. In many cases, systematic development of the LJ interaction parameters in a CG model requires a comprehensive sampling of the objective molecules at the all-atom (AA) level, which is therefore extremely time-consuming for large systems. Inspired by the concept of electrostatic potential (ESP), we define the LJ static potential (LJSP), by which the embedding potential energy surface can be constructed analytically. A semianalytic approach, namely, the LJSP matching method, is developed here to derive the CG parameters by minimizing the LJSP difference between the AA and the CG models, which provides a universal way to derive the CG LJ parameters from the AA models without doing presampling. The LJSP matching method is successful not only in deriving the LJ interaction energy landscape in the CG models for proteins, lipids, and DNA but also in reproducing the critical properties such as intermediate structures and enthalpy contributions as exemplified in simulating the self-assembly process of the dipalmitoylphosphatidylcholine (DPPC) lipids.
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http://dx.doi.org/10.1021/acs.jctc.2c00513DOI Listing
August 2022

A rare case of recurrent primary dumbbell-shaped spinal hydatidosis.

Radiol Case Rep 2022 Sep 1;17(9):3224-3227. Epub 2022 Jul 1.

Lanzhou University Second Hospital, Lanzhou, Gansu 730000, China.

Spinal hydatidosis, which affects the thoracic vertebrae, is not only an extremely rare occurrence, but is also characterized by a high recurrence rate. Here, we reported a case of 67-years-old man who presented with recurrent spinal hydatid disease. The condition was originally misdiagnosed as Schwannoma via medical imaging, but eventually confirmed by postoperative pathology. He was subjected to surgery, combined with adjuvant drug therapy. Unfortunately, he experienced recurrent spinal hydatid disease and had to undergo hydatid cyst excision in over 5 years.
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http://dx.doi.org/10.1016/j.radcr.2022.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256548PMC
September 2022

Long noncoding RNA MIR210HG is induced by hypoxia-inducible factor 1α and promotes cervical cancer progression.

Am J Cancer Res 2022 15;12(6):2783-2797. Epub 2022 Jun 15.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University Guangzhou 510515, Guangdong, P. R. China.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1α (HIF-1α). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1α decreased each other's expression level, while silencing MIR210HG or HIF-1α respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1α knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1α can activate the transcription of MIR210HG via binding its promoter. Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1α contributing to cervical carcinogenesis, with potential implications for therapeutic targeting.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251695PMC
June 2022

Maternal Consumption of Milk or Dairy Products During Pregnancy and Birth Outcomes: A Systematic Review and Dose-Response Meta-Analysis.

Front Nutr 2022 9;9:900529. Epub 2022 Jun 9.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

Purpose: This study aimed to systematically review current evidence and quantitatively evaluate the associations between milk or dairy consumption during pregnancy and birth outcomes.

Methods: This systematic review had been reported in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A supplementary literature search in PubMed, Web of Science, Cochrane Library, and Embase was conducted on 30 March 2021. Studies that assessed the association of maternal consumption of milk or dairy with birth-related outcomes were identified. The dose-response meta-analyses of continuous data and categorical data were applied. One-stage approach and two-stage approach were used where appropriate.

Results: In total, 42 studies were eligible for the present systematic review, and 18 of them were included in the outcome-specific meta-analyses. The dose-response meta-analysis [Number of studies () = 9] predicted a maximum mean change in birthweight of 63.38 g [95% Confidence Interval (CI) = 0.08, 126.67] at 5.00 servings per day. Intake of dairy products had the greatest protective effect on small for gestational age at a maximum of 7.2 servings per day [Relative risk (RR) = 0.69, 95% CI = 0.56, 0.85] ( = 7). The risk of large for gestational age was predicted to be maximum at 7.20 servings per day of dairy consumption, with the RR and 95% CI of 1.30 (1.15, 1.46; = 4). In addition, the relationship between dairy consumption and low birth weight (RR = 0.70, 95% CI = 0.33, 1.50; = 5) and pre-mature birth (RR = 1.13, 95% CI = 0.87, 1.47; = 5) was not significant, respectively.

Conclusions: Maternal consumption of dairy during pregnancy has a potential effect on fetal growth. Further well-designed studies are warranted to clarify the specific roles of individual dairy products.

Systematic Review Registration: identifier: PROSPERO 2020 CRD42020150608.
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http://dx.doi.org/10.3389/fnut.2022.900529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261982PMC
June 2022

Editorial: The Pivotal Role of Oral Microbiota Dysbiosis and Microbiota-Host Interactions in Diseases.

Front Cell Infect Microbiol 2022 14;12:947638. Epub 2022 Jun 14.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.3389/fcimb.2022.947638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267765PMC
July 2022

Transcriptional activation of budding yeast DDI2/3 through chemical modifications of Fzf1.

Cell Biol Toxicol 2022 Jul 9. Epub 2022 Jul 9.

Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada.

DDI2 and DDI3 (DDI2/3) are two identical genes in Saccharomyces cerevisiae encoding cyanamide (CY) hydratase. They are not only highly induced by CY, but also by a DNA-damaging agent methyl methanesulfonate (MMS), and the regulatory mechanism is unknown. In this study, we performed a modified genome-wide genetic synthetic array screen and identified Fzf1 as a zinc-finger transcriptional activator required for CY/MMS-induced DDI2/3 expression. Fzf1 binds to a DDI2/3 promoter consensus sequence CS2 in vivo and in vitro, and this interaction was enhanced in response to the CY treatment. Indeed, experimental over production of Fzf1 alone was sufficient to induce DDI2/3 expression; however, CY and MMS treatments did not cause the accumulation or apparent alteration in migration of cellular Fzf1. To test a hypothesis that Fzf1 is activated by covalent modification of CY and MMS, we performed mass spectrometry of CY/MMS-treated Fzf1 and detected a few modified lysine residues. Amino acid substitutions of these residues revealed that Fzf1-K70A completely abolished MMS-induced and reduced CY-induced DDI2/3 expression, indicating that the Fzf1-K70 methylation activates Fzf1. This study collectively reveals a novel regulatory mechanism by which Fzf1 is activated by chemical modifications and in turn induces the expression of its target genes for detoxification.
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http://dx.doi.org/10.1007/s10565-022-09745-xDOI Listing
July 2022
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