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1.
Bone ; 182: 117050, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38367924

RESUMEN

Postmenopausal osteoporosis (PMOP) is a common kind of osteoporosis that is associated with excessive osteocyte death and bone loss. Previous studies have shown that TNF-α-induced osteocyte necroptosis might exert a stronger effect on PMOP than apoptosis, and TLR4 can also induce cell necroptosis, as confirmed by recent studies. However, little is known about the relationship between TNF-α-induced osteocyte necroptosis and TLR4. In the present study, we showed that TNF-α increased the expression of TLR4, which promoted osteocyte necroptosis in PMOP. In patients with PMOP, TLR4 was highly expressed at skeletal sites where exists osteocyte necroptosis, and high TLR4 expression is correlated with enhanced TNF-α expression. Osteocytes exhibited robust TLR4 expression upon exposure to necroptotic osteocytes in vivo and in vitro. Western blotting and immunofluorescence analyses demonstrated that TNF-α upregulated TLR4 expression in vitro, which might further promote osteocyte necroptosis. Furthermore, inhibition of TLR4 by TAK-242 in vitro effectively blocked osteocyte necroptosis induced by TNF-α. Collectively, these results suggest a novel TLR4-mediated process of osteocyte necroptosis, which might increase osteocyte death and bone loss in the process of PMOP.


Asunto(s)
Osteocitos , Osteoporosis Posmenopáusica , Receptor Toll-Like 4 , Factor de Necrosis Tumoral alfa , Femenino , Humanos , Necroptosis , Osteocitos/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
2.
Acta Otorhinolaryngol Ital ; 44(2): 83-90, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38165205

RESUMEN

Objective: This study aimed to investigate the global research status, hot topics, and prospects in the field of sinonasal inverted papilloma (SNIP) through bibliometric analysis. Methods: The literature on SNIP was retrieved and downloaded from the Web of Science Core Collection from 2002 to 2021. The bibliometric and visualisation networks of SNIP were constructed using VOSviewer 1.6.18, CiteSpace 6.1. R2, and a bibliometric online analysis platform. Results: A total of 560 original articles about SNIP research were included, involving 2,457 authors from 610 institutions in 45 countries. The number of SNIP publications showed an overall rising trend, with an average annual output of 28 articles and almost 3 times as many articles published in 2020 as in 2002. The analysis of keyword burst detection indicated that EGFR mutation, malignant transformation and infection are emerging research hotspots. Moreover, EGFR mutation, KRAS mutation, malignant tumour, metallothionein 2a gene, pre-operative diagnosis, HPV-negative tumour, and expression were among the 11 key clusters of co-cited references. Conclusions: This study provided a comprehensive, systematic, and objective analysis and visualised knowledge map of SNIP over the past 2 decades. In particular, current hotspots and prospective trends in the field of SNIP have been identified. These results highlight the future direction of SNIP research for rhinologists.


Asunto(s)
Bibliometría , Papiloma Invertido , Neoplasias de los Senos Paranasales , Papiloma Invertido/patología , Humanos , Neoplasias de los Senos Paranasales/patología , Investigación Biomédica , Factores de Tiempo
3.
Technol Cancer Res Treat ; 23: 15330338231216333, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38258400

RESUMEN

BACKGROUND: RAD51 is a central protein involved in homologous recombination, which has been linked to cancer development and progression. systemic inflammatory indicator markers such as neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio have also been implicated in cancer. However, the relationship between Rad51 and these inflammatory markers in esophageal cancer patients undergoing esophagectomy is not yet understood. METHODS: We retrospectively observed 320 esophageal cancer patients who underwent esophagectomy. We collected clinical characteristics, postoperative complications, and survival analysis data and analyzed the relationship between Rad51 expression, inflammatory markers, and prognosis. RESULTS: We found significant linear relationships among the inflammatory markers. There were also close relationships between Rad51 expression and neutrophil-to-lymphocyte ratio or C-reactive protein. Patients with low lymphocyte percentage were more likely to have low Rad51 expression (P = .026), high C-reactive protein (P = .007), and high neutrophil-to-lymphocyte ratio (P = .006). Low lymphocyte-to-monocyte ratio was associated with poor overall survival and was an independent prognostic factor (HR = 2.214; 95% confidence interval: 1.044-4.695, P = .038). In patients without lymph node metastases, low albumin (HR= 0.131; 95% confidence interval: 0.025-0.687, P = .016), high neutrophil-to-lymphocyte ratio (HR = 0.002; 95% confidence interval: 0.000-0.221, P = .009), and high Rad51 expression (HR = 14.394; 95% confidence interval: 2.217-97.402, P = .006) were associated with poor overall survival. CONCLUSIONS: Our study found a close correlation between elevated Rad51 expression and inflammatory markers. High Rad51 expression, high neutrophil-to-lymphocyte ratio, and low lymphocyte-to-monocyte ratio are associated with lower survival rates. The combined assessment of Rad51 and inflammatory markers can be useful for preoperative assessment and prognostic evaluation in esophageal squamous cell carcinoma patients.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Proteína C-Reactiva , Pronóstico , Estudios Retrospectivos
4.
Biochem Pharmacol ; 219: 115939, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38000560

RESUMEN

Carfilzomib, a second-generation proteasome inhibitor, has been approved as a treatment for relapsed and/or refractory multiple myeloma. Nevertheless, the molecular mechanism by which Carfilzomib inhibits esophageal squamous cell carcinoma (ESCC) progression largely remains to be determined. In the present study, we found that Carfilzomib demonstrated potent anti-tumor activity against esophageal squamous cell carcinoma both in vitro and in vivo. Mechanistically, carfilzomib triggers mitochondrial apoptosis and reprograms cellular metabolism in ESCC cells. Moreover, it has been identified that activating transcription factor 3 (ATF3) plays a crucial cellular target role in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively antagonized the effects of carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, the ATF3 protein is specifically bound to lactate dehydrogenase A (LDHA) to effectively suppress LDHA-mediated metabolic reprogramming in response to carfilzomib treatment. Research conducted in xenograft models demonstrates that ATF3 mediates the anti-tumor activity of Carfilzomib. The examination of human esophageal squamous cell carcinoma indicated that ATF3 and LDHA have the potential to function as innovative targets for therapeutic intervention in the treatment of ESCC. Our findings demonstrate the novel function of Carfilzomib in modulating ESCC metabolism and progression, highlighting the potential of Carfilzomib as a promising therapeutic agent for the treatment of ESCC.


Asunto(s)
Factor de Transcripción Activador 3 , Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Oligopéptidos , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Oligopéptidos/farmacología , Línea Celular Tumoral , Antineoplásicos/farmacología , Xenoinjertos , Trasplante de Neoplasias , Humanos , Animales , Ratones , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Apoptosis , Reprogramación Metabólica/efectos de los fármacos , Factor de Transcripción Activador 3/metabolismo
5.
Front Neurol ; 14: 1270989, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38107637

RESUMEN

Vestibular schwannomas in pregnancy have rarely been reported, and there is a lack of in-depth discussion on the experience of management of massive acoustic neuromas in pregnancy. Herein, we present a pregnant woman with a giant vestibular schwannoma and obstructive hydrocephalus who presented at 30 weeks of gestation. She was initially misdiagnosed as having a pregnancy-related reaction of headache, dizziness, and vomiting that had occurred 2 months earlier. After observation at home, her symptoms progressed at 30 weeks of gestation, and imaging findings revealed a brain tumor in the CPA region with secondary cerebella tonsil herniation and obstructive hydrocephalus, and she was transferred to our center for treatment. Consequently, we relieved her hydrocephalus with a ventriculoperitoneal shunt (V-P shunt) and used corticosteroids to simulate fetal maturation. After 10 days, her mental condition deteriorated, and her right limb muscle strength gradually decreased until grade 0 (MMT Grading). Finally, under a joint consultation with the Department of Neurosurgery, Obstetrics, and Anesthesiology, she underwent a cesarean section under general anesthesia and first-stage tumor removal at 31 weeks of gestation. Upon discharge, the previously observed neurological deficits, which were reversible and had manifested during her gestational period, had been successfully resolved, and the fetus had been conserved. The neuroimaging confirmed the complete tumor removal, while the neuropathologic examination revealed a vestibular schwannoma. Therefore, we recommend early diagnosis and treatment for these patients, especially people with headaches, vomiting, and sudden hearing loss during pregnancy. Herein, we concluded that our cases provide a valuable experience in the latest acceptable time frame for the operation to prevent irreversible neurological impairment and premature delivery in late pregnancy.

6.
Infect Drug Resist ; 16: 5637-5645, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37662977

RESUMEN

Purpose: The emergence of resistant strains has greatly reduced the eradication rate of H. pylori (HP) in conventional bismuth-containing quadruple therapy. Meanwhile, the new 7-day dual therapy with vonoprazan (VPZ) and amoxicillin (AMO) failed to achieve the expected therapeutic effect in China. Patients and Methods: A total of 256 untreated HP-infected patients are included in this non-inferiority clinical trial. The patients were randomly divided into three groups: 14-day dual therapy group (VPZ 20mg b.i.d + AMO 750mg t.i.d for 14 days, VA14), 14-day modified triple therapy group (VA14 + Jinghua Weikang Capsule 160mg t.i.d, VAC), and conventional bismuth-containing quadruple therapy group for 14 days (BCQ). Eradication rates, drug-related adverse events (AEs), patient compliance, and drug costs were compared among the three groups. Results: The eradication rates in the BCQ, VA14, and VAC were 78.67, 77.33%, and 86.49% by intention-to-treat analysis, respectively, and 96.72%, 90.63%, and 92.75% by pre-protocol or modified intention-to-treat analysis, respectively. VA14 therapy indicated a non-inferiority eradication rate and advanced safety and economics to BCQ therapy. JWC further improved the eradication rate and reduced the incidence of AEs. Conclusion: A modified 14-day dual therapy with VPZ and AMO provides satisfied efficacy as the first-line treatment for HP infection in China.

7.
Front Neurosci ; 17: 1259889, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37746148

RESUMEN

Hearing impairment is a global health problem. Stem cell therapy has become a cutting-edge approach to tissue regeneration. In this review, the recent advances in stem cell therapy for hearing loss have been discussed. Nanomaterials can modulate the stem cell microenvironment to augment the therapeutic effects further. The potential of combining nanomaterials with stem cells for repairing and regenerating damaged inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) has also been discussed. Stem cell-derived exosomes can contribute to the repair and regeneration of damaged tissue, and the research progress on exosome-based hearing loss treatment has been summarized as well. Despite stem cell therapy's technical and practical limitations, the findings reported so far are promising and warrant further investigation for eventual clinical translation.

8.
J Transl Med ; 21(1): 605, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37679788

RESUMEN

BACKGROUND: Glycolysis under normoxic conditions, known as the Warburg effect, confers a selective advantage for the survival and proliferation of many tumors. In this study, we investigated the role of estrogen-related receptor gamma (ESRRG) in metabolic reprogramming in esophageal squamous cell carcinoma (ESCC). METHODS: Bioinformatics analysis indicated that ESRRG expression was decreased in ESCC tissue and associated with poor clinical outcomes. We also examined the effects of altered ESRRG expression on the proliferation and metabolic reprogramming of ESCC cells. We explored the impact of ESRRG on Pyruvate kinase M2 (PKM2) expression and malignant behavior in ESCC. RESULTS: Our study revealed the inhibitory effects of ESRRG on the growth, tumorigenesis, and glycolysis activity of ESCC cells, which were mediated by the downregulation of PKM2 expression. We further demonstrated that ESRRG directly interacts with the PKM2 promoter to inhibit its activity in ESCC. Notably, the ESRRG-specific agonist, DY131, inhibited ESCC cell proliferation and glycolysis activity by modulating genes in the glycolysis pathway. Moreover, we verified that DY131 exhibits enhanced activity as an immune checkpoint inhibitor, considering the significance of the ESRRG-PKM2 axis in the lactate regulation of ESCC cells. CONCLUSION: Our findings provide novel insights into the role of ESRRG-PKM2 signaling in regulating ESCC cell metabolism and immune checkpoint regulation. Additionally, we suggest that DY131 holds promise as a promising therapeutic agent for ESCC treatment.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Regulación hacia Abajo , Carcinogénesis , Ácido Láctico , Receptores de Estrógenos
9.
J Orthop Surg (Hong Kong) ; 31(2): 10225536231175237, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37144863

RESUMEN

BACKGROUND: Prosthetic-joint infection (PJI) is one of the severest complications after arthroplasty. However, antibiotics are not effective in the bacteria in biofilm outside the prosthetic-joint. Antimicrobial peptides have an efficient antimicrobial activity in staphylococcus aureus compared with conventional antibiotics. METHODS: Bone marrow stem cells (BMSCs) were isolated, cultured and transfected with cathelicidins antimicrobial peptides proline-arginine-rich 39 amino acid peptide (PR-39) lentivirus. The expression of PR-39 gene in BMSCs was detected by RT-PCR, and the antibacterial activity of PR-39 was measured by agar diffusion method. The transfection efficiency was detected by fluorescence microscopy. The infection model of artificial knee joint in rabbits were established. Kirschner wire was used as the knee joint implant to implant the distal femur through the femoral intercondylar fossa of rabbits. 24 rabbits were randomly divided into 2 groups for the above operations: group A was inoculated 0.5 mL into the joint cavity immediately after the incision was sutured 1 × 107 Staphylococcus aureus of colony forming unit (CFU), group B was inoculated with Staphylococcus aureus and PR-39. After operation, the wound conditions and histological changes were observed by X-ray and optical microscope respectively, CRP and erythrocyte sedimentation rate were measured by test assay. RESULTS: The transfection efficiency of lentivirus vectortransfected BMSCs was 74.09%. The supernatant of lentivirus vector had obvious inhibitory effect on Staphylococcus aureus, and the antibacterial rate was 98.43%. 100% infection observed in group A while few infection observed in group B; serum CRP and ESR at a high level in group A while decreased in group B after operation. There were no significant difference in CRP and ESR between the pLV/PR-39 group and pLV/EGFP group at day 1 and 3 respectively after surgery. However, CRP and ESR in the pLV/PR-39 groupwere significantly lower than the pLV/EGFP group at day 7 and 14 respectively after operation. CONCLUSIONS: Rabbits planted BMSCs expressing PR-39 were significantly increased resistance to Staphylococcus aureus in PJI than control group thus showing great potential for preventing implant-associated infection. It will provide a potential new therapeutic agent for implant-associated infection.


Asunto(s)
Infecciones Relacionadas con Prótesis , Infecciones Estafilocócicas , Animales , Conejos , Catelicidinas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus , Infecciones Relacionadas con Prótesis/prevención & control
10.
BMC Gastroenterol ; 23(1): 153, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37189078

RESUMEN

BACKGROUND: Next-generation sequencing (NGS) is maturely applied for gene fusion detection. Although tumor fusion burden (TFB) has been identified as an immune marker for cancer, the relationship between these fusions and the immunogenicity and molecular characteristics of gastric cancer (GC) patients remains unclear. GCs have different clinical significance depending on their subtypes, and thus, this study aimed to investigate the characteristics and clinical relevance of TFB in non-Epstein-Barr-virus-positive (EBV+) GC with microsatellite stability (MSS). METHODS: A total of 319 GC patients from The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and a cohort of 45-case from ENA (PRJEB25780) were included. The cohort characteristics and distribution of TFB among the patients were analyzed. Additionally, the correlations of TFB with mutation characteristics, pathway differences, relative abundance of immune cells, and prognosis were examined in the TCGA-STAD cohort of MSS and non-EBV (+) patients. RESULTS: We observed that in the MSS and non-EBV (+) cohort, the TFB-low group exhibited significantly lower gene mutation frequency, gene copy number, loss of heterozygosity score, and tumor mutation burden than in the TFB-high group. Additionally, the TFB-low group exhibited a higher abundance of immune cells. Furthermore, the immune gene signatures were significantly upregulated in the TFB-low group, 2-year disease-specific survival was markedly increased in the TFB-low group compared with to the TFB-high group. The rates of TFB-low cases were significantly higher TFB-than high cases in durable clinical benefit (DCB) and response groups with pembrolizumab treatment. Low TFB may serve as a predictor of GC prognosis, and the TFB-low group exhibits higher immunogenicity. CONCLUSION: In conclusion, this study reveals that the TFB-based classification of GC patient may be instructive for individualized immunotherapy regimens.


Asunto(s)
Adenocarcinoma , Infecciones por Virus de Epstein-Barr , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Relevancia Clínica , Pronóstico , Mutación , Adenocarcinoma/patología
11.
Suicide Life Threat Behav ; 53(3): 484-498, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36946602

RESUMEN

OBJECTIVE: We aimed to identify and understand risk and protective factors for suicide among South Korean females by linking survey and social media data and using interpretable machine learning approaches. MATERIALS AND METHODS: We collected a wide range of potential factors including the material, psychosocial, and behavioral data from a detailed survey, which we then linked to data from social media. In addition, we adopted interpretable machine learning approaches to (1) predict the suicide risk, (2) explain the relative importance of factors and their interactions regarding suicide, and (3) understand individual differences affecting suicide risk. RESULTS: The best-performing machine learning model achieved an AUC of 0.737. Adverse childhood experiences, social connectedness, and mean positive sentiment score of social media posts were the three risk factors that had a monotonic or unimodal relationship with suicide, and satisfaction with life, narcissistic self-presentation, and number of close friends on social media were the three protective factors that had a monotonic or unimodal relationship with suicide. We also found several meaningful interactions between specific psychiatric symptoms and narcissistic self-presentation. CONCLUSIONS: Our findings can help governmental organizations to better assess female suicide risk in South Korea and develop more informed and customized suicide prevention strategies.


Asunto(s)
Medios de Comunicación Sociales , Suicidio , Humanos , Femenino , Factores Protectores , Suicidio/psicología , Aprendizaje Automático , República de Corea
12.
J Med Internet Res ; 25: e43521, 2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36656626

RESUMEN

BACKGROUND: An increasing number of medical journals are using social media to promote themselves and communicate with their readers. However, little is known about how medical journals use Twitter and what their social media management strategies are. OBJECTIVE: This study aimed to understand how medical journals use Twitter from a global standpoint. We conducted a broad, in-depth analysis of all the available Twitter accounts of medical journals indexed by major indexing services, with a particular focus on their social networks and content. METHODS: The Twitter profiles and metadata of medical journals were analyzed along with the social networks on their Twitter accounts. RESULTS: The results showed that overall, publishers used different strategies regarding Twitter adoption, Twitter use patterns, and their subsequent decisions. The following specific findings were noted: journals with Twitter accounts had a significantly higher number of publications and a greater impact than their counterparts; subscription journals had a slightly higher Twitter adoption rate (2%) than open access journals; journals with higher impact had more followers; and prestigious journals rarely followed other lesser-known journals on social media. In addition, an in-depth analysis of 2000 randomly selected tweets from 4 prestigious journals revealed that The Lancet had dedicated considerable effort to communicating with people about health information and fulfilling its social responsibility by organizing committees and activities to engage with a broad range of health-related issues; The New England Journal of Medicine and the Journal of the American Medical Association focused on promoting research articles and attempting to maximize the visibility of their research articles; and the British Medical Journal provided copious amounts of health information and discussed various health-related social problems to increase social awareness of the field of medicine. CONCLUSIONS: Our study used various perspectives to investigate how medical journals use Twitter and explored the Twitter management strategies of 4 of the most prestigious journals. Our study provides a detailed understanding of medical journals' use of Twitter from various perspectives and can help publishers, journals, and researchers to better use Twitter for their respective purposes.


Asunto(s)
Medicina , Medios de Comunicación Sociales , Humanos , Factor de Impacto de la Revista , Metadatos , Red Social
13.
Arch Suicide Res ; 27(1): 13-28, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34319221

RESUMEN

In this study, we implemented machine learning models that can detect suicidality posts on Twitter. We randomly selected and annotated 20,000 tweets and explored metadata and text features to build effective models. Metadata features were studied in great details to understand their possibility and importance in suicidality detection models. Results showed that posting type (i.e., reply or not) and time-related features such as the month, day of the week, and the time (AM vs. PM) were the most important metadata features in suicidality detection models. Specifically, the probability of a social media post being suicidal is higher if the post is a reply to other users rather than an original tweet. Moreover, tweets created in the afternoon, on Fridays and weekends, and in fall have higher probabilities of being detected as suicidality tweets compared with those created in other times. By integrating metadata and text features, we obtained a model of good performance (i.e., F1 score of 0.846) that can assist humans in the real-world setting to detect suicidality social media posts.


Asunto(s)
Medios de Comunicación Sociales , Suicidio , Humanos , Metadatos , Ideación Suicida , Aprendizaje Automático
15.
FASEB J ; 36(12): e22625, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36331546

RESUMEN

Renal fibrosis, a common pathological manifestation of virtually all types of chronic kidney disease (CKD), ultimately predisposes patients to end-stage renal disease. However, there is no effective therapy for renal fibrosis. Our earlier studies proved that RIP3-mediated necroptosis might be an important mode of renal tubular cell death in rats with chronic renal injury. Under transmission electron microscopy (TEM), we found morphological changes in the necrosis of human renal tissue, and the percentage of necrotic cells increased significantly in patients with stages 2 and 3a CKD. Immunofluorescence analyses showed that the percentages of TUNEL+ /RIP3+ double-positive and TUNEL+ /MLKL+ double-positive tubular epithelial cells in renal tubules of patients with stages 2 and 3a CKD were significantly increased compared to those in control patients without renal disease. Immunohistochemistry analyses of renal biopsy specimens from patients with CKD revealed RIP3, MLKL, and p-MLKL upregulation in patients with stages 2 and 3a CKD, suggesting that necroptosis of renal tubular epithelial cells in CKD patients occurs, and the peak of necroptosis was in stages 2 and 3a CKD. We showed that profibrotic factor proteins (TGF-ß1, Smad2 and Smad3) and fibroblast activation markers (α-SMA and Vimentin) were specifically upregulated in stage 2 and 3a CKD patients. In addition, Pearson correlation analysis showed that the percentage of necroptotic renal tubular epithelial cells was positively correlated with TGF-ß1 and collagen-I. We also showed that RIP1/3 or MLKL inhibitors decreased the expression of RIP3, MLKL, TGF-ß1, and Smad3 in HK-2 cells treated with TNF-α. FGF-2, α-SMA, Vimentin and FN were overexpressed in the hRIFs cultured with the supernatant of necroptotic HK-2 cells, whereas necroptosis blockers (Nec-1s, GSK'872 and NSA) and TGF-ß1/Smad3 pathway antagonists (LY364947 and SIS3) reduced FGF-2, α-SMA, Vimentin and FN levels. Collectively, necroptosis of renal tubular epithelial cells in CKD patients occurs, and the peak of necroptosis was in stages 2 and 3a CKD. Renal tubular epithelial cell necroptosis mediates renal tubulointerstitial fibrosis in patients with chronic kidney disease, which is related to the TGF-ß1/Smad3 signaling pathway.


Asunto(s)
Insuficiencia Renal Crónica , Factor de Crecimiento Transformador beta1 , Humanos , Ratas , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Necroptosis , Vimentina/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibrosis , Células Epiteliales/metabolismo , Insuficiencia Renal Crónica/metabolismo , Riñón/metabolismo , Necrosis/patología
16.
Front Public Health ; 10: 1022790, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388317

RESUMEN

Introduction: Studies have shown that suicide is closely related to various social factors. However, due to the restriction in the data scale, our understanding of these social factors is still limited. We propose a conceptual framework for understanding social determinants of suicide at the national level and investigate the relationships between structural determinants (i.e., gender, employment statuses, and occupation) and suicide outcomes (i.e., types of suicide, places of suicide, suicide methods, and warning signs) in South Korea. Methods: We linked a national-level suicide registry from the Korea Psychological Autopsy Center with the Social Determinants of Health framework proposed by the World Health Organization's Commission on Social Determinants of Health. Results: First, male and female suicide victims have clear differences in their typical suicide methods (fire vs. drug overdose), primary warning signs (verbal vs. mood), and places of death (suburb vs. home). Second, employees accounted for the largest proportion of murder-suicides (>30%). The proportion of students was much higher for joint suicides than for individual suicides and murder-suicides. Third, among individuals choosing pesticides as their suicide method, over 50% were primary workers. In terms of drug overdoses, professionals and laborers accounted for the largest percentage; the former also constituted the largest proportion in the method of jumping from heights. Conclusion: A clear connection exists between the investigated structural factors and various suicide outcomes, with gender, social class, and occupation all impacting suicide.


Asunto(s)
Suicidio , Humanos , Masculino , Femenino , Suicidio/psicología , Factores Sociales , Determinantes Sociales de la Salud , República de Corea/epidemiología , Clase Social
17.
Neoplasma ; 69(6): 1314-1321, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36264776

RESUMEN

Esophageal squamous cell carcinoma (ESCC) has limited effective treatment strategies. DNA damage response (DDR) genes are of therapeutic interest in multiple cancer types. This study aimed to depict the landscape of DDR mutations in ESCC and evaluate the association between DDR mutations and known immunotherapy biomarkers. We recruited 250 Chinese patients with ESCC and performed next-generation sequencing. A total of 107 patients underwent a PD-L1 examination. Among the 250 patients, 73 (29.2%) harbored at least one DDR gene mutation and were defined as DDR-mut. Among the six functional DDR pathways, homologous recombination (HR) accounted for 12.4% (31/250). DDR-mut patients were significantly associated with higher tumor mutational burden than those in the DDR-wt group (p=7.4e-07). Patients with PDL1-H accounted for 21.2% (36/107) of the patients. PDL1-H was more prevalent in DDR-mut than DDR-wt, although the p-value did not reach a significant level (40.5% vs. 30%, p=0.29). Further analysis revealed that BRCA1, one of the most frequently mutated genes in the HR pathway, was significantly associated with PDL1-H (p=0.01). Our data revealed a subset of patients with ESCC harbored DDR gene mutations. Patients with these DDR gene mutations are significantly associated with immune biomarkers, implying the potential feasibility of combining DDR agents with immunotherapy in patients with DDR deficiency.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Neoplasias Esofágicas/patología , Mutación , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Daño del ADN
19.
BMC Nephrol ; 23(1): 271, 2022 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-35907795

RESUMEN

BACKGROUND: We report a case of a patient who suffered thrombosis of a radial artery-cephalic vein fistula accompanied by aneurysm and a single outflow path of the elbow perforating vein. We performed open surgery combined with Fogarty balloon catheter embolectomy, anastomotic reconstruction and forearm median vein transposition. CASE PRESENTATION: The patient presented with an arteriovenous fistula (AVF) after haemodialysis 5 years ago. In the process of dialysis, the fistula vein was punctured, resulting in aneurysm, high pressure and difficult haemostasis after needle extraction. AVF occlusion was observed on April 12, 2022. We performed a combined open surgery. First, a Fogarty balloon catheter was used to remove the thrombus, and the anastomosis was then reconstructed to restore AVF fistula patency. Finally, forearm median vein transposition was used to establish dual outflow. Postoperative haemodialysis was possible. There are various methods for removing the thrombus in AVF. Here, we report a case in which we performed open surgery combined with Fogarty balloon catheter embolectomy, anastomotic reconstruction and forearm median vein transposition to ensure fistula patency. CONCLUSION: We removed a complete reverse 'Z'-shaped thrombus of the elbow perforating vein in a haemodialysis fistula. This report provides an effective strategy to manage a high-pressure fistula with single outflow of the elbow perforating vein.


Asunto(s)
Aneurisma , Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Trombosis , Derivación Arteriovenosa Quirúrgica/efectos adversos , Derivación Arteriovenosa Quirúrgica/métodos , Codo/irrigación sanguínea , Humanos , Diálisis Renal , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/cirugía , Resultado del Tratamiento , Grado de Desobstrucción Vascular
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