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2.
Front Cell Infect Microbiol ; 14: 1402389, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39380726

RESUMO

Introduction: Genitourinary syndrome of menopause (GSM) describes the symptoms and signs resulting from the effect of estrogen deficiency on the female genitourinary tract, including genital, urinary, and sexual symptoms. However, besides estrogen deficiency, little is known about the etiology of GSM. The objective of this study was to investigate the effects of vaginal microbiota dysbiosis on the occurrence and development of GSM in perimenopausal and postmenopausal women. Methods: In total, 96 women were enrolled in this cross-sectional study and clinical data were collected. GSM symptoms were divided into three types: genital, urological, and sexual symptoms. Full-length 16S rRNA gene sequencing using the third-generation PacBio sequencing technology was performed to analyze the vaginal microbiome using vaginal swabs of non-GSM and GSM women with different types of GSM symptoms. Live Lactobacillus Capsule for Vaginal Use (LLCVU) treatment was used to verify the effects of Lactobacillus on GSM symptoms. Results: We found that 83.58% (56/67) of women experienced GSM symptoms in the perimenopausal and postmenopausal stages. Among these women with GSM, 23.21% (13/56), 23.21% (13/56), and 53.57% (30/56) had one type, two types, and three types of GSM symptoms, respectively. The richness and diversity of vaginal microbiota gradually increased from reproductive to postmenopausal women. There were significant differences in vaginal microbial community among non-GSM women and GSM women with different types of symptoms. Lactobacillus was found to be negatively associated with the onset, severity, and type of GSM while some bacteria, such as Escherichia-shigella, Anaerococcus, Finegoldia, Enterococcus, Peptoniphilus_harei, and Streptococcus, were found to be positively associated with these aspects of GSM, and these bacteria were especially associated with the types of genital and sexual symptoms in GSM women. LLCVU significantly relieved genital symptoms and improved the sexual life of GSM women in shortterm observation. Conclusions: The onset, severity, and type of GSM symptoms may be associated with changes in vaginal microbiota in perimenopausal and postmenopausal women. Vaginal microbiota dysbiosis probably contributes to the occurrence and development of GSMsymptoms, especially vaginal and sexual symptoms. Lactobacillus used in the vagina may be a possible option for non-hormonal treatment of GSM women with genital and sexual symptoms. Clinical Trial Registration: https://www.chictr.org.cn/indexEN.html, identifier ChiCTR2100044237.


Assuntos
Disbiose , Lactobacillus , Menopausa , Microbiota , RNA Ribossômico 16S , Vagina , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Estudos Transversais , Disbiose/microbiologia , Doenças Urogenitais Femininas/microbiologia , Lactobacillus/isolamento & purificação , Lactobacillus/genética , Pós-Menopausa , RNA Ribossômico 16S/genética , Síndrome , Vagina/microbiologia
3.
Investig Clin Urol ; 65(5): 459-465, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39249918

RESUMO

PURPOSE: To investigate the relationship between prostatic urethral angle (PUA) and the development of surgical capsule calculi (SCC) within the prostate, and to examine the presence and impact of intravesical prostatic protrusion (IPP). MATERIALS AND METHODS: A retrospective analysis was conducted on 90 patients who underwent radical prostatectomy, with preoperative assessments using both transrectal ultrasound of the prostate (TRUS) and magnetic resonance imaging. Patients were divided into groups with and without SCC and further categorized into type 1 and type 2 stones based on the location and severity of the calculi. Statistical analysis included chi-square and independent sample t-tests, with p<0.05 considered significant. RESULTS: Of the patients, 82.2% were diagnosed with SCC. No significant difference in PUA was found between patients with and without SCC. However, a notable disparity in IPP presence was observed, suggesting an inverse correlation with SCC development. Additionally, no significant differences were identified when comparing the two types of SCC based on PUA and IPP measurements. CONCLUSIONS: The presence of IPP exhibited an inverse relationship with SCC, suggesting diminished urine flow pressure over the prostatic urethra may reduce the likelihood of SCC formation. However, no direct association between PUA and the presence or severity of SCC was identified. These findings highlight the complexity of factors contributing to prostatic calculi development and the potential role of IPP in this context.


Assuntos
Próstata , Prostatectomia , Uretra , Humanos , Masculino , Estudos Retrospectivos , Uretra/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Prostatectomia/métodos , Próstata/patologia , Próstata/diagnóstico por imagem , Doenças Prostáticas/diagnóstico por imagem , Doenças Prostáticas/patologia , Cálculos/diagnóstico por imagem
4.
Zhen Ci Yan Jiu ; 49(8): 814-820, 2024 Aug 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39318310

RESUMO

OBJECTIVES: To observe the effect of ginger-salt-partitioned moxibustion on ATP-sensitive potassium (KATP) channel of bladder in detrusor overactivity (DO) rats. METHODS: Female SD rats were randomly divided into sham operation, model, moxibustion and antagonist groups (n=9 in each group). Thorax (T) 10 spinal cord transection was performed by surgery. Ginger-salt partitioned moxibustion was applied to "Shenque" (CV8) for 3 cones, once daily for 14 consecutive days. Rats of the antagonist group were intraperitoneally injected with KATP channel specific antagonist glibenclamide (10 µg·kg-1·d-1) once daily for 14 consecutive days. Urodynamic tests were performed after treatment. The distribution and expression of KATP channel tetrameric subunit (SUR2B) in the bladder of rats was observed by immunofluorescence. The protein and mRNA expression levels of SUR2B in bladder tissue were detected by Western blot and qPCR respectively. RESULTS: Compared with the sham operation group, rats of the model group showed intensive and large phasic contractions of the detrusor during bladder filling, the frequency and amplitude of phasic contractions of the detrusor 5 min before leakage were significantly increased (P<0.001);the voiding threshold pressure was significantly decreased (P<0.001);the bladder perfusion volume was increased (P<0.001);the SUR2B protein and mRNA expression in bladder tissue were significantly reduced (P<0.001). Compared with the model group and the antagonist group, the above-mentioned indicators in the moxibustion group were all reversed (P<0.01, P<0.001, P<0.05). CONCLUSIONS: Ginger-salt partitioned moxibustion can reduce the frequency and amplitude of detrusor phase contraction during bladder filling and prolong the time of first phase contraction in DO rats, which may be associated with up-regulating the expression level of KATP channel protein and mRNA, promoting the outflow of potassium ions, and inhibiting the inflow of calcium ions, thus improve the stability of detrusor during storage.


Assuntos
Pontos de Acupuntura , Canais KATP , Moxibustão , Ratos Sprague-Dawley , Bexiga Urinária Hiperativa , Bexiga Urinária , Animais , Feminino , Ratos , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/terapia , Bexiga Urinária Hiperativa/metabolismo , Bexiga Urinária Hiperativa/genética , Bexiga Urinária Hiperativa/fisiopatologia , Canais KATP/metabolismo , Canais KATP/genética , Humanos
5.
Zhen Ci Yan Jiu ; 49(8): 787-796, 2024 Aug 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39318307

RESUMO

OBJECTIVES: To observe the effect of electroacupuncture on miR-142-5p and ADAMTS1/PI3K/AKT pathway in rats with ischemic stroke, so as to explore the regulatory mechanism of electroacupuncture on angiogenesis after ischemic stroke. METHODS: This study was divided into two parts. The first part of the experiment:SD rats were randomly divided into sham operation group, model group and electroacupuncture group. There were 20 rats in each group. The middle cerebral artery occlusion (MCAO) rat model was prepared using a modified Longa's method. In the electroacupuncture group, "Shuigou" (GV26) was selected for electroacupuncture intervention (4 Hz/20 Hz) for 30 min each time. The rats in the electroacupuncture group were given electroacupuncture immediately after successful modeling, once a day for 4 times. Hunter score and TTC staining were used to observe the neurological deficits and infarct volumes respectively;HE staining was used to observe the cortical pathological changes;immunohistochemistry was used to determine the changes of cerebral microvascular density. Real-time quantitative PCR and Western blot were used to observe the miR-142-5p expression, mRNA and protein expression levels of ADAMTS1, VEGF, PI3K, AKT, eNOS in ischemic cortex. The second part of the experiment:The rats were randomly divided into electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group with 8 rats in each group. MCAO model was established after injection. Electroacupuncture+control group was given 0.9% sodium chloride solution injected into the right ventricle.The rats in the electroacupuncture+miR-142-5p Antagomir group were injected with miR-142-5p inhibitor into the right ventricle 30 min before modeling. Rats in electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group were all given the same electroacupuncture treatment. Real-time fluorescence quantitative PCR was used to observe the effect of miR-142-5p Antagomir on the expression of miR-142-5p and ADAMTS1 mRNA. The effect of miR-142-5p Antagomir on ADAMTS1 protein was observed by Western blot. RESULTS: In the first part of the experiment, compared with the sham operation group, the Hunter score in the model group was significantly increased (P<0.01);the volume of cerebral infarction in the model group was significantly increased (P<0.01);the degree of brain edema and neuronal necrosis and the density of cerebral microvessels was increased;the cerebral microvascular density was significantly increased (P<0.01);the expression levels of miR-142-5p and the mRNA expression levels of VEGF, AKT and eNOS were significantly decreased (P<0.01, P<0.05), and the protein expression levels of VEGF, p-AKT and eNOS were significantly down-regulated (P<0.01), while the mRNA expression levels of ADAMTS1 and PI3K, and the protein expression levels of ADAMTS1 and p-PI3K were all up-regulated (P<0.01, P<0.05) in the model group. Compared with the model group, after intervention, the Hunter score in the electroacupuncture group was decreased (P<0.01), the volume of cerebral infarction was significantly decreased (P<0.01);the degree of brain edema and neuronal necrosis were alleviated;the cerebral microvascular density was significantly increased (P<0.01);the expression of miR-142-5p and the mRNA expression of VEGF, PI3K, AKT and eNOS were increased (P<0.01), the protein expressions of VEGF, p-PI3K, p-AKT and eNOS were increased (P<0.01, P<0.05), while the mRNA and protein expression of ADAMTS1 were decreased (P<0.05, P<0.01). After injection of miR-142-5p inhibitor, compared with electroacupuncture+control group, the expression of miR-142-5p in electroacupuncture+miR-142-5p Antagomir group was decreased(P<0.05), while the mRNA and protein expression of ADAMTS1 were increased (P<0.01, P<0.05). CONCLUSIONS: Electroacupuncture at GV26 can improve the neurological damage of ischemic stroke rats, reduce the volume of cerebral infarction and promote angiogenesis. The mechanism may be associated with the function of electroacupuncture in promoting the expression of miR-142-5p, so as to inhibit the expression of its target gene ADAMTS1, mediate the up-regulation of VEGF expression, activate PI3K/AKT pathway, promote the release of eNOS, and participate in promoting angiogenesis in ischemic stroke rats.


Assuntos
Proteína ADAMTS1 , Eletroacupuntura , MicroRNAs , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Acidente Vascular Cerebral , Animais , Ratos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Masculino , Proteína ADAMTS1/genética , Proteína ADAMTS1/metabolismo , Humanos , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Transdução de Sinais , Neovascularização Fisiológica/genética , Angiogênese
6.
Pestic Biochem Physiol ; 204: 106101, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277423

RESUMO

Riptortus pedestris (Hemiptera: Alydidae), a common agricultural pest, is the major causative agent of "soybean staygreen." However, the interactions between chemosensory proteins (CSPs) in R. pedestris and host plant volatiles have yet to be comprehensively studied. In this study, we performed real-time fluorescence quantitative polymerase chain reaction (PCR) to analyze the antennal expression of RpedCSP22 and subsequently analyzed the interactions between 21 soybean volatiles, five aggregation pheromones, and RpedCSP22 protein in vitro using a protein expression system, molecular docking, site-directed mutagenesis, and fluorescence competitive binding experiments. The RpedCSP22 protein showed binding affinity to three soybean volatiles (benzaldehyde, 4-ethylbenzaldehyde, and 1-octene-3-ol), with optimal binding observed under neutral pH conditions, and lost binding ability after site-directed mutagenesis. In subsequent RNA interference (RNAi) studies, gene silencing was more than 90 %, and in silenced insects, electroantennographic responses were reduced by more than 75 % compared to non-silenced insects. Moreover, Y-tube olfactory behavioral assessments revealed that the attraction of R. pedestris to the three soybean volatiles was significantly attenuated. These findings suggest that RpedCSP22 plays an important role in the recognition of host plant volatiles by R. pedestris andprovides a theoretical basis for the development of novel inhibitors targeting pest behavior.


Assuntos
Glycine max , Proteínas de Insetos , Compostos Orgânicos Voláteis , Animais , Glycine max/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/química , Compostos Orgânicos Voláteis/metabolismo , Mutagênese Sítio-Dirigida , Simulação de Acoplamento Molecular , Hemípteros/metabolismo , Hemípteros/genética , Antenas de Artrópodes/metabolismo , Feromônios/metabolismo , Heterópteros/metabolismo , Heterópteros/genética
7.
Phys Chem Chem Phys ; 26(37): 24689-24698, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39282755

RESUMO

Mixed ionic-electronic conductors are widely used as electroactive materials in energy applications. The contact of a mixed conductor with another phase plays a crucial role in charge storage and transport in energy devices. However, the interfacial chemistry at the heterojunctions comprising mixed conductors and its interplay with the bulk chemistry remains imperative yet inadequately understood. This study addresses the fundamentals of space charge effects by exploring the equilibrium situations for contacts consisting of mixed conductors. From the perspective of defect chemistry, and by unifying the bulk and interfacial conditions with the electrochemical potential, our treatment allows for predicting the built-in potential at heterojunctions, profiling the space charge distributions, and evaluating the resulting interfacial charge storage and transport. The treatment can be related to experimental characterization, including coulometric titration, conductivity, and capacitance measurements at electrochemical interfaces in all-solid-state batteries. Besides, our treatment also highlights the significance of size and doping effects in nanocrystalline electrodes. This work provides a comprehensive framework for understanding and engineering the heterojunctions in electrochemical devices.

8.
Int Immunopharmacol ; 142(Pt A): 113053, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39260307

RESUMO

Abnormally elevated tumor necrosis factor-α (TNFα) levels at the maternal-fetal interface can lead to adverse pregnancy outcomes, including recurrent miscarriage (RM), but the mechanism underlying upregulated TNFα expression is not fully understood. We previously reported that the interaction between monoclonal nonspecific suppressor factor-ß (MNSFß) and RC3H1 upregulates TNFα expression, but the precise mechanisms are unknown. In this study, we found that MNSFß stimulated the LPS-induced TNFα expression by inactivating the promoting effect of RC3H1 on TNFα mRNA degradation rather than directly inhibiting the expression of RC3H1 in THP1-Mϕs. Mechanistically, the 81-326 aa region of the RC3H1 protein binds to the 101-133 aa region of the MNSFß protein, and MNSFß facilitated stress granules (SGs) formation and the translocation of RC3H1 to SGs by interacting with RC3H1 and fragile X mental retardation 1 (FMR1) in response to LPS-induced stress. The SGs-localization of RC3H1 reduced its inhibitory effect on TNFα expression in LPS-treated THP1-Mϕs. The designed HEPN2 peptide effectively reduced the LPS-induced expression of TNFα in THP1-Mϕs by interfering with the MNSFß-RC3H1 interaction. Treatment with the HEPN2 peptide significantly improved adverse pregnancy outcomes, including early pregnancy loss (EPL) and lower fetal weight (LFW), which are induced by LPS in mice. These data indicated that MNSFß promoted TNFα expression at least partially by increasing the localization of RC3H1 to SGs under inflammatory stimulation and that the HEPN2 peptide improved the adverse pregnancy outcomes induced by LPS in mice, suggesting that MNSFß is a potential pharmacological target for adverse pregnancy outcomes caused by abnormally increased inflammation at early pregnancy.


Assuntos
Lipopolissacarídeos , Macrófagos , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/metabolismo , Animais , Humanos , Feminino , Gravidez , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Grânulos de Estresse/metabolismo , Aborto Habitual/metabolismo , Aborto Habitual/imunologia , Camundongos Endogâmicos C57BL , Peptídeos/farmacologia , Células THP-1
9.
Mayo Clin Proc ; 99(9): 1374-1387, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39115507

RESUMO

OBJECTIVE: To assess the effects of colchicine, which has been shown to reduce the risks of coronary artery disease but scarcely studied in peripheral artery disease (PAD), on major adverse limb events (MALE) in patients with PAD. METHODS: This is a retrospective study based on a nationwide database. Patients who were diagnosed with PAD between 2010 and 2020 and prescribed with colchicine after the diagnosis of PAD were identified. Patients were then categorized into the colchicine or the control group according to drug use. Propensity score matching was performed to mitigate selection bias. Risks of MALE (including lower limb revascularization and nontraumatic amputation) and major adverse cardiovascular events were compared between the two groups. RESULTS: After patient selection and propensity score matching, there were 60,219 patients in both colchicine and control groups. After a mean follow-up of 4.5 years, the risk of MALE was significantly lower in the colchicine group compared with control (subdistribution HR, 0.75; 95% CI, 0.71 to 0.80), as were the incidence of both components of MALE, lower limb revascularization and major amputations. Colchicine treatment was also associated with lower risk of cardiovascular death. The lower risk of MALE observed with colchicine therapy was accentuated in the subgroup of patients receiving concomitant urate-lowering medications. CONCLUSION: In patients diagnosed with PAD, the use of colchicine is associated with lower risks of MALE and cardiovascular death. Anti-inflammatory therapy with colchicine may provide benefits in vascular beds beyond the coronary arteries.


Assuntos
Colchicina , Doença Arterial Periférica , Humanos , Colchicina/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Masculino , Estudos Retrospectivos , Idoso , Feminino , Pessoa de Meia-Idade , Pontuação de Propensão , Amputação Cirúrgica/estatística & dados numéricos , Extremidade Inferior/irrigação sanguínea , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia
10.
Front Cell Infect Microbiol ; 14: 1430302, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099883

RESUMO

Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/µl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Leite Humano , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e Especificidade , Humanos , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Leite Humano/virologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , Feminino , Recém-Nascido , Fatores de Tempo
11.
Clin Pharmacol Ther ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148369

RESUMO

Although the benefits of sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) are well established, patients with hemodynamically significant mitral regurgitation (MR) were excluded from pivotal trials. We aimed to assess the effects of sacubitril/valsartan on survival in patients with HFrEF and concomitant significant MR. All patients from a single center who underwent echocardiography between June 2008 and December 2020, with a left ventricular ejection fraction (LVEF) of less than 40% and hemodynamically significant MR were recruited. Patients were categorized according to drug use and year of the index echocardiogram into the angiotensin receptor/neprilysin inhibitor (ARNI), non-ARNI before 2017, and non-ARNI after 2017 groups. Patients in the ARNI and non-ARNI after 2017 groups were compared directly, whereas patients in the non-ARNI before 2017 group were matched to the ARNI group in a 3:1 ratio. The outcome of interest was all-cause mortality. Death was compared between the groups using univariate and multivariate Cox proportional hazard models. After exclusion by criteria and matching, there remained 610 patients in the ARNI group, 434 in the non-ARNI after 2017 group, and 1,722 in the non-ARNI before 2017 group. During follow-up, all-cause mortality was significantly lower in the ARNI group compared with both non-ARNI after 2017 and non-ARNI before 2017 groups. Multivariate analysis of both pairs of comparison between groups found the use of ARNI to be significantly associated with increased survival. In patients with HFrEF and concomitant significant MR, treatment with sacubitril/valsartan was associated with lower risks of all-cause death.

12.
J Alzheimers Dis ; 100(s1): S305-S325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39093074

RESUMO

Background: The September 11, 2001, catastrophe unleashed widespread destruction beyond the World Center (WTC), with fires and toxic gases leaving lasting impacts. First responders at Ground Zero faced prolonged exposure to hazardous particulate matter (PM), resulting in chronic health challenges. Among the multitude of health concerns, the potential association between the WTCPM and Alzheimer's disease (AD) has emerged as an area of intense inquiry, probing the intricate interplay between environmental factors and neurodegenerative diseases. Objective: We posit that a genetic predisposition to AD in mice results in dysregulation of the gut-brain axis following chronic exposure to WTCPM. This, in turn, may heighten the risk of AD-like symptoms in these individuals. Methods: 3xTg-AD and WT mice were intranasally administered with WTCPM collected at Ground Zero within 72 hours after the attacks. Working memory and learning and recognition memory were monitored for 4 months. Moreover, brain transcriptomic analysis and gut barrier permeability along with microbiome composition were examined. Results: Our findings underscore the deleterious effects of WTCPM on cognitive function, as well as notable alterations in brain genes associated with synaptic plasticity, pro-survival, and inflammatory signaling pathways. Complementary, chronic exposure to the WTCPM led to increased gut permeability in AD mice and altered bacteria composition and expression of functional pathways in the gut. Conclusions: Our results hint at a complex interplay between gut and brain axis, suggesting potential mechanisms through which WTCPM exposure may exacerbate cognitive decline. Identifying these pathways offers opportunities for tailored interventions to alleviate neurological effects among first responders.


Assuntos
Doença de Alzheimer , Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Camundongos Transgênicos , Material Particulado , Ataques Terroristas de 11 de Setembro , Animais , Camundongos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Eixo Encéfalo-Intestino/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Masculino
13.
Artigo em Inglês | MEDLINE | ID: mdl-39143404

RESUMO

PURPOSE: The goal of this meta-analysis is to examine the association between Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) in patients with Retinal Artery Occlusion (RAO). The analysis aims to provide insight into the potential of NLR and PLR as inflammatory biomarkers for RAO. METHODS: Following PRISMA guidelines, a systematic search in PubMed, Embase, and Scopus identified eight eligible studies. The analysis assessed serum NLR and PLR levels in RAO and non-RAO groups by employing standardized mean differences (SMDs). Sensitivity analyses and publication bias were examined. The diagnostic performance of these markers was evaluated with a quantitative synthesis. RESULTS: The meta-analysis, involving 1,444 participants, demonstrated significantly elevated NLR (SMD = 0.88, 95% CI: 0.49-1.28, P < 0.001) and PLR (SMD = 0.45, 95% CI: 0.16-0.73, P < 0.001) levels in individuals with RAO. Significant heterogeneity was noted. Sensitivity analysis showed robustness and no significant publication bias was found. Summary results of diagnostic performance revealed promising discriminatory power for NLR and PLR. CONCLUSIONS: The results support a possible connection between systemic inflammation, as indicated by NLR and PLR, and the occurrence of RAO. Although there was heterogeneity, sensitivity analyses showed the findings to be robust. While immediate diagnostic applications are limited, understanding the role of NLR and PLR in the pathological process of RAO provides valuable insights for developing future predictive models, risk management approaches, and treatment strategies. Further research exploring mechanistic insights and conducting prospective studies is warranted to validate their clinical utility. KEY MESSAGES: What is known Retinal artery occlusion (RAO) is a serious condition with potential links to systemic inflammation and thrombosis. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are emerging inflammatory markers. What is new This is the first meta-analysis examining the association between NLR, PLR and RAO. Elevated NLR and PLR levels were observed in patients with RAO compared to controls. NLR and PLR show potential as indicators of systemic inflammation in RAO pathogenesis.

14.
Clin Res Cardiol ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158600

RESUMO

OBJECTIVES: To delineate the effects of exposure to air pollution on the risk of venous thromboembolism (VTE). BACKGROUND: The association between air pollution and arterial occlusive diseases has been well reported in the literature. VTE is the third most common acute cardiovascular syndrome; however, its relationship with exposure to air pollution has been controversial. METHODS: This study linked data from the Taiwan National Health Insurance Research Database with that from the Taiwan Environmental Protection Administration. Patients who were first admitted for VTE between January 1, 2001, and December 31, 2013, were analyzed. A time-stratified, case-crossover design was employed. Three different exposure periods were defined: exposure for 1 month, one quarter, and 1 year. Four control periods were designated for each exposure period. The association between exposure to air pollutants and the risk of VTE was tested using logistic regression analysis. Subgroup analyses were also performed, stratified by age, sex, type of VTE, the use of hormone therapy, and level of urbanization at the site of residence. RESULTS: Exposures to particulate matter (PM) smaller than 2.5 µm (PM2.5) and those smaller than 10 µm (PM10) were associated with higher risks of VTE, with longer exposures associated with higher risk. The concentration of PM2.5 exposure for 1 month was linearly associated with a greater risk of VTE up to 28.0 µg/m3, beyond which there was no association. PM2.5 exposure for one quarter or 1 year remained significantly associated with higher risks of VTE at higher concentrations. The increased risk in VTE associated with exposure to PM2.5 was more prominent in older patients and in patients not under hormone therapy. Similar results were observed for PM10 exposures. CONCLUSIONS: Exposure to PM, particularly PM2.5, leads to an increased risk of VTE, with possible accumulative effects. With increased PM production in industrializing countries, the effects of PM on VTE occurrence warrant further attention.

15.
Medicina (Kaunas) ; 60(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39064513

RESUMO

Background and Objectives: This paper evaluates the efficacy and safety of ureteral access sheath (UAS) utilization in retrograde intrarenal surgery (RIRS). Materials and Methods: We searched PubMed, Embase, and the Cochrane Library up to 30 August 2023. The inclusion criteria comprised English-language original studies on RIRS with or without UAS in humans. The primary outcome was SFR, while the secondary outcomes included intraoperative and postoperative complications, the lengths of the operation and the hospitalization period, and the duration of the fluoroscopy. Subgroup analyses and a sensitivity analysis were performed. Publication bias was assessed using funnel plots and Egger's regression tests. Dichotomous variables were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs), while mean differences (MDs) were employed for continuous variables. Results: We included 22 studies in our analysis. These spanned 2001 to 2023, involving 12,993 patients and 13,293 procedures. No significant difference in SFR was observed between the UAS and non-UAS groups (OR = 0.90, 95% CI 0.63-1.30, p = 0.59). Intraoperative (OR = 1.13, 95% CI 0.75-1.69, p = 0.5) and postoperative complications (OR = 1.29, 95% CI 0.89-1.87, p = 0.18) did not significantly differ between the groups. UAS usage increased operation times (MD = 8.30, 95% CI 2.51-14.10, p = 0.005) and fluoroscopy times (MD = 5.73, 95% CI 4.55-6.90, p < 0.001). No publication bias was detected for any outcome. Conclusions: In RIRS, UAS usage did not significantly affect SFR, complications, or hospitalization time. However, it increased operation time and fluoroscopy time. Routine UAS usage is not supported, and decisions should be patient-specific. Further studies with larger sample sizes and standardized assessments are needed to refine UAS utilization in RIRS.


Assuntos
Ureter , Humanos , Ureter/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Duração da Cirurgia , Rim/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricos , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Tempo de Internação/estatística & dados numéricos
16.
World J Clin Cases ; 12(19): 3985-3994, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38994293

RESUMO

BACKGROUND: Myeloid sarcoma (MS), also referred to as granulocytic sarcoma or chloroma, is a rare type of extramedullary malignant tumor. MS comprises primitive granulocytic precursor cells that play a key role in the early stages of white blood cell development. Notably, the occurrence of this tumor in the gingiva is rare. CASE SUMMARY: The present study reported the case of MS with gingival swelling in the maxillary region, with aleukemic presentation in a 32-year-old male patient. Following two courses of chemotherapy, computed tomography of the region demonstrated complete clearance of the tumor. At the 12-month follow-up appointment, the patient was in a stable condition with the absence of progression. The etiology, clinical features, diagnosis, and relevant treatment of MS are discussed in the present study. CONCLUSION: Diagnosis of MS may be confirmed following histological and immunohistochemical examinations.

18.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38975895

RESUMO

Spatial transcriptomics provides valuable insights into gene expression within the native tissue context, effectively merging molecular data with spatial information to uncover intricate cellular relationships and tissue organizations. In this context, deciphering cellular spatial domains becomes essential for revealing complex cellular dynamics and tissue structures. However, current methods encounter challenges in seamlessly integrating gene expression data with spatial information, resulting in less informative representations of spots and suboptimal accuracy in spatial domain identification. We introduce stCluster, a novel method that integrates graph contrastive learning with multi-task learning to refine informative representations for spatial transcriptomic data, consequently improving spatial domain identification. stCluster first leverages graph contrastive learning technology to obtain discriminative representations capable of recognizing spatially coherent patterns. Through jointly optimizing multiple tasks, stCluster further fine-tunes the representations to be able to capture complex relationships between gene expression and spatial organization. Benchmarked against six state-of-the-art methods, the experimental results reveal its proficiency in accurately identifying complex spatial domains across various datasets and platforms, spanning tissue, organ, and embryo levels. Moreover, stCluster can effectively denoise the spatial gene expression patterns and enhance the spatial trajectory inference. The source code of stCluster is freely available at https://github.com/hannshu/stCluster.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Algoritmos , Humanos , Animais , Software , Aprendizado de Máquina
19.
Stroke ; 55(8): 2151-2162, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38946544

RESUMO

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.


Assuntos
AVC Isquêmico , Camundongos Knockout , Neurônios , Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/agonistas , Camundongos , AVC Isquêmico/metabolismo , Masculino , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Reabilitação do Acidente Vascular Cerebral , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BL
20.
J Dig Dis ; 25(6): 380-393, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38992957

RESUMO

OBJECTIVES: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , China/epidemiologia , Criança , Masculino , Feminino , Inquéritos e Questionários , Adulto , Padrões de Prática Médica/estatística & dados numéricos , Atitude do Pessoal de Saúde , Competência Clínica , Pessoa de Meia-Idade , Médicos de Atenção Primária , Pediatras/estatística & dados numéricos , Médicos
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