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1.
PLoS One ; 19(5): e0303494, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771764

RESUMO

PURPOSE: To identify the predictive role of sarcopenia in long-term survival among rectal cancer patients who underwent surgery based on available evidence. METHODS: The Medline, EMBASE and Web of Science databases were searched up to October 20, 2023, for relevant studies. Overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) were the endpoints. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the association between sarcopenia and survival. RESULTS: Fifteen studies with 4283 patients were included. The pooled results demonstrated that preoperative sarcopenia significantly predicted poorer OS (HR = 2.07, 95% CI = 1.67-2.57, P<0.001), DFS (HR = 1.85, 95% CI = 1.39-2.48, P<0.001) and CSS (HR = 1.83, 95% CI = 1.31-2.56, P<0.001). Furthermore, subgroup analysis based on neoadjuvant therapy indicated that sarcopenia was a risk factor for worse OS and DFS in patients who received (OS: HR = 2.44, P<0.001; DFS: HR = 2.16, P<0.001) but not in those who did not receive (OS: HR = 2.44, P<0.001; DDFS: HR = 1.86, P = 0.002) neoadjuvant chemoradiotherapy. In addition, subgroup analysis based on sample size and ethnicity showed similar results. CONCLUSION: Preoperative sarcopenia is significantly related to poor survival in surgical rectal cancer patients and could serve as a novel and valuable predictor of long-term prognosis in these patients.


Assuntos
Neoplasias Retais , Sarcopenia , Sarcopenia/mortalidade , Sarcopenia/complicações , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/mortalidade , Neoplasias Retais/complicações , Intervalo Livre de Doença , Terapia Neoadjuvante , Prognóstico , Período Pré-Operatório , Fatores de Risco
2.
Zhen Ci Yan Jiu ; 49(5): 512-518, 2024 May 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38764123

RESUMO

OBJECTIVES: To explore the therapeutic effect of Fu's subcutaneous needling at myofascial trigger points (MTrPs) on pain, lumbar mobility and the quality of life in patients with lumbar disc herniation (LDH), so as to provide clinicians with new ideas and methods in treating LDH. METHODS: One hundred patients with LDH admitted to department of rehabilitation medicine of the affiliated hospital of Chengdu University of Traditional Chinese Medicine from January 2022 to January 2023 were collected as the subjects, and they were randomly divided into an observation group and a control group, 50 cases in each one. In the observation group, the spreading technique of Fu's subcutaneous needling was delivered at MTrP. In the control group, the routine acupuncture was applied to Shenshu (BL23), Weizhong (BL40) and MTrP. The treatment was given 3 times weekly, for 2 weeks in the two groups. The score of visual analogue scale (VAS) was evaluated before treatment, at the moment after the 1st treatment completion and after 2 weeks of treatment, separately, and the inclinometer was adopted to measure the range of motion (ROM) of the lumbar flexion, extension and lateral flexion. The numbers of MTrPs and their distribution were recorded before treatment and after the completion of a 2-week treatment in the two groups. Before treatment and in 4 weeks of follow-up, using SF-36 scale, the score of the quality of life was evaluated. The incidence of adverse effects was recorded. RESULTS: At the moment of the 1st treatment completion and after 2 weeks of treatment, VAS score and ROM of the lumbar region were significantly improved in comparison with those before treatment in the two groups and the improvement was superior in the observation group compared with the control group (P<0.05, P<0.01). After 2 weeks of treatment, the total number of MTrPs and the counts of MTrPs in each muscle zone were reduced when compared with those before treatment (P<0.05). In the observation group, the total number of MTrPs and numbers of MTrPs in the zones of quadratus lumborum, musculi multifidus and musculi iliocostalis lumborum decreased significantly when compared with the control group (P<0.05), while the difference was not significant in the numbers in the zone of musculi glutaeus medius between the two groups. In 4 weeks of follow-up, the scores of SF-36 scale were improved in comparison with those before treatment in each group and the result in the observation was better (P<0.05). No any adverse events occurred during treatment in the two groups. CONCLUSIONS: Fu's subcutaneous needling is effective for reducing the numbers of MTrPs and improving analgesia, ROM of the lumbar region, as well as the long-term quality of life in the patients with LDH.


Assuntos
Terapia por Acupuntura , Deslocamento do Disco Intervertebral , Vértebras Lombares , Qualidade de Vida , Pontos-Gatilho , Humanos , Deslocamento do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/fisiopatologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pontos-Gatilho/fisiopatologia , Vértebras Lombares/fisiopatologia , Resultado do Tratamento , Pontos de Acupuntura
3.
FEBS Open Bio ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740554

RESUMO

Glioblastoma (GBM) poses a significant challenge in oncology and stands as the most aggressive form of brain cancer. A primary contributor to its relentless nature is the stem-like cancer cells, called glioblastoma stem cells (GSCs). GSCs have the capacity for self-renewal and tumorigenesis, leading to frequent GBM recurrences and complicating treatment modalities. While natural killer (NK) cells exhibit potential in targeting and eliminating stem-like cancer cells, their efficacy within the GBM microenvironment is limited due to constrained infiltration and function. To address this limitation, novel investigations focusing on boosting NK cell activity against GSCs are imperative. This study presents two streamlined image-based assays assessing NK cell migration and cytotoxicity towards GSCs. It details protocols and explores the strengths and limitations of these methods. These assays could aid in identifying novel targets to enhance NK cell activity towards GSCs, facilitating the development of NK cell-based immunotherapy for improved GBM treatment.

4.
Environ Pollut ; 351: 124061, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679131

RESUMO

Diffusive gradients in thin films technique (DGT) is recognized as a more reliable method for determining labile heavy metal (HM) concentration in soil than traditional destructive methods. However, the current DGT measurement index, CDGT, theoretically underestimates the true labile concentration (Clabile) of HMs in soil and lacks direct comparability with the conventional soil HM content indices due to unit differences. Here, we proposed CDGT-W, a new simple index which is defined as the HM accumulation in the binding layer, normalized to the weight of soil (optimized water content = 100% of the maximum water holding capacity) filled in the open cavity-type DGT device over a specified deployment time (optimized time = 24 h). The procedure for measuring CDGT-W is analogous to that of CDGT but includes precise determination of water content (water/dry soil) and the mass of soil filled in the cavity. We conducted measurements of Cu, Pb, Cr(Ⅵ) and As(V) as CDGT-W, CDGT, solution concentration (Csoln), and CaCl2 extractable concentration (CCaCl2) on three soils with a diverse range of HM concentrations. CDGT-W showed significant linear correlations with all other tested indexes. The ratios of CDGT-W to CCaCl2 varied between 0.30 and 0.98 for all HM-soil combinations with only one exception, a range much greater than CDGT/Csoln (typically <0.1) but lower than 1. This suggested that CDGT-W may more accurately reflect Clabile than CDGT (theoretically underestimates Cliable) and CCaCl2(likely overestimates Cliable). Additionally, CDGT-W measurements for these four HMs exhibited a broad measure concentration range and a low detection limit (mg/kg level). Consequently, CDGT-W may offer a more reliable alternative to CDGT for characterizing Clabile in unsaturated soils.

5.
Environ Sci Pollut Res Int ; 31(21): 30959-30971, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38619769

RESUMO

Soil amendment is an important strategy for improving soil quality and crop yield. From 2014 to 2019, we conducted a study to investigate the effects of tobacco straw return with lime on soil nutrients, soil microbial community structure, tobacco leaf yield, and quality in southern Anhui, China. A field experiment was conducted with four treatments: straw removed (CK), straw return (St), straw return with dolomite (St + D), and straw return with lime (St + L). Results showed that after 5 years of application, the St + L significantly increased the soil pH by 16.9%, and the contents of soil alkaline nitrogen (N) and available potassium (K) by 17.2% and 23.0%, respectively, compared with the CK. Moreover, the St + L significantly increased tobacco leaf yield (24.0%) and the appearance (9.1%) and sensory (5.9%) quality of flue-cured tobacco leaves. The addition of soil conditioners (straw, dolomite, and lime) increased both the total reads and effective sequences of soil microorganisms. Bacterial diversity was more sensitive to changes in the external environment compared to soil fungi. The application of soil amendments (lime and straw) promoted the growth of beneficial microorganisms in the soil. Additionally, bacterial species had greater competition and limited availability of resources for survival compared to fungi. The results showed that soil microorganisms were significantly influenced by the presence of AK, AN, and pH contents. These findings can provide an effective method for improving the quality of flue-cured tobacco leaves and guiding the amelioration of acidic soil in regions where tobacco-rice rotation is practiced.


Assuntos
Compostos de Cálcio , Nicotiana , Óxidos , Folhas de Planta , Microbiologia do Solo , Solo , Solo/química , Compostos de Cálcio/farmacologia , Compostos de Cálcio/química , Microbiota/efeitos dos fármacos , Agricultura/métodos , China
6.
PLoS One ; 19(3): e0299125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478532

RESUMO

BACKGROUND: To synthesize the existing evidence on the association between obesity and rotator cuff repair outcomes such as pain, shoulder function, range of motion, and complications. METHODS: We searched PubMed, EMBASE, and Scopus databases for relevant observational studies (cohort and case-control) and randomized controlled trials (RCTs). The target population in the included studies comprised adults who had undergone rotator cuff repair procedures. The outcomes of interest were functional outcomes (such as range of motion), pain scores, patient-reported outcome measures, and complication rates (such as re-repair and readmission rates). We applied random-effects models and calculated pooled effect sizes reported as standardized mean differences (SMDs) or relative risks (RRs) with 95% confidence intervals. RESULTS: We analysed data from 11 studies. In most, the follow-up periods ranged from 12 to 60 months. Obese individuals experienced greater pain (SMD 0.30; 95% CI, 0.10, 0.50) and lower shoulder function (SMD -0.33; 95% CI, -0.54, -0.12) than other individuals in the long-term post-operative follow-up. Obese individuals also had higher risks of complications (RR 1.48; 95% CI, 1.11, 1.98) and readmission (RR 1.35; 95% CI, 1.27, 1.43), but a similar likelihood of re-repair (RR, 1.27; 95% CI, 0.82, 1.95) than non-obese/normal BMI individuals. While the forward flexion and external rotation functions were comparable, obese individuals displayed less internal rotation function than other individuals (SMD -0.59; 95% CI, -0.87, -0.30). CONCLUSION: Obesity was associated with unfavourable outcomes after rotator cuff surgery, including increased pain, reduced shoulder function, high risks of complications, and readmission. These findings emphasize the importance of addressing obesity-related factors to improve post-operative outcomes.


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Adulto , Humanos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/cirurgia , Ombro , Dor de Ombro/complicações , Amplitude de Movimento Articular , Artroscopia/métodos , Obesidade/complicações , Resultado do Tratamento
7.
Clin Transl Immunology ; 13(3): e1498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481614

RESUMO

Objectives: For children with Kawasaki disease (KD) at high risk of developing coronary artery lesions and requiring retreatment with intravenous immunoglobulin (IVIG), the availability of accurate prediction models remains limited because of inconsistent variables and unsatisfactory prediction results. We aimed to construct models to predict patient's probability of IVIG retreatment combining children's individual inflammatory characteristics. Methods: Clinical manifestations and laboratory examinations of 266 children with KD were retrospectively analysed to build a development cohort data set (DC) and a validation cohort data set (VC). In the DC, binary logistic regression analyses were performed using R language. Nomograms and receiver operating curves were plotted. The concordance index (C index), net reclassification index, integrated discrimination improvement index and confusion matrix were applied to evaluate and validate the models. Results: Models_5V and _9V were established. Both contained variables including the percentages of CD8+ T cells, CD4+ T cells, CD3+ T cells, levels of interleukin (IL)-2R and CRP. Model_9V additionally included variables for IL-6, TNF-α, NT-proBNP and sex, with a C index of 0.86 (95% CI 0.79-0.92). When model_9V was compared with model_5V, the NRI and IDI were 0.15 (95% CI 0.01-0.30, P < 0.01) and 0.07 (95% CI 0.02-0.12, P < 0.01). In the VC, the sensitivity, specificity and precision of model_9V were 1, 0.875 and 0.667, while those of model_5V were 0.833, 0.875 and 0.625. Conclusion: Model_9V combined cytokine profiles and lymphocyte subsets with clinical characteristics and was superior to model_5V achieving satisfactory predictive power and providing a novel strategy early to identify patients who needed IVIG retreatment.

8.
J Neurol Sci ; 459: 122953, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490090

RESUMO

OBJECTIVE: Status epilepticus (SE) in the neurology intensive care unit (ICU) is associated with significant morbidity. We aimed to evaluate the utility of existing prognostic scores, namely the Status Epilepticus Severity Score (STESS), Epidemiology Based Mortality Score in Status Epilepticus (EMSE)-EACE and Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT), among SE patients in the neurology ICU. METHODS: Neurology ICU patients with SE requiring continuous electroencephalography (cEEG) monitoring over a 10 year period were included. The STESS, EMSE-EACE and END-IT scores were applied retrospectively. Receiver operating characteristic (ROC) analysis was performed to assess the discriminatory value of the scores for inpatient mortality and functional decline, as measured by increase in the modified Rankin Scale (mRS) on discharge. RESULTS: Eighty-five patients were included in the study, of which 71 (83.5%) had refractory SE. Inpatient mortality was 36.5%. Sixty - seven (78.8%) of patients suffered functional decline, with a median mRS of 5 upon hospital discharge. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with inpatient mortality were 0.723 (95% CI 0.613-0.833), 0.722 (95% CI 0.609-0.834) and 0.560 (95% CI 0.436-0.684) respectively. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with functional decline were 0.604 (95% CI 0.468-0.741), 0.596 (95% CI 0.439-0.754) and 0.477 (95% CI 0.331-0.623). SIGNIFICANCE: SE was associated with high mortality and morbidity in this cohort of neurology ICU patients requiring cEEG monitoring. The STESS and EMSE-EACE scores had acceptable AUCs for prediction of inpatient mortality. However, the STESS, EMSE-EACE and END-IT were poorly-correlated with discharge functional outcomes. Further refinements of the scores may be necessary among neurology ICU patients for predicting discharge functional outcomes.


Assuntos
Unidades de Terapia Intensiva , Estado Epiléptico , Humanos , Estudos Retrospectivos , Prognóstico , Índice de Gravidade de Doença , Estado Epiléptico/diagnóstico
9.
Nanoscale ; 16(14): 6876-6899, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38506154

RESUMO

The use of nanocarriers for drug delivery has opened up exciting new possibilities in cancer treatment. Among them, calcium carbonate (CaCO3) nanocarriers have emerged as a promising platform due to their exceptional biocompatibility, biosafety, cost-effectiveness, wide availability, and pH-responsiveness. These nanocarriers can efficiently encapsulate a variety of small-molecule drugs, proteins, and nucleic acids, as well as co-encapsulate multiple drugs, providing targeted and sustained drug release with minimal side effects. However, the effectiveness of single-drug therapy using CaCO3 nanocarriers is limited by factors such as multidrug resistance, tumor metastasis, and recurrence. Combination therapy, which integrates multiple treatment modalities, offers a promising approach for tackling these challenges by enhancing efficacy, leveraging synergistic effects, optimizing therapy utilization, tailoring treatment approaches, reducing drug resistance, and minimizing side effects. CaCO3 nanocarriers can be employed for combination therapy by integrating drug therapy with photodynamic therapy, photothermal therapy, sonodynamic therapy, immunotherapy, radiation therapy, radiofrequency ablation therapy, and imaging. This review provides an overview of recent advancements in CaCO3 nanocarriers for drug delivery and combination therapy in cancer treatment over the past five years. Furthermore, insightful perspectives on future research directions and development of CaCO3 nanoparticles as nanocarriers in cancer treatment are discussed.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Sistemas de Liberação de Medicamentos/métodos , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico , Terapia Combinada , Nanopartículas/metabolismo
10.
Heliyon ; 10(6): e28066, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524612

RESUMO

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

11.
Biomolecules ; 14(3)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38540767

RESUMO

Mitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairment through urinary donor-derived cell-free mitochondrial DNA (ddcfmtDNA), addressing the crucial challenge of BKPyVAN diagnosis. Urinary samples were collected at the time of biopsy from a total of 60 kidney transplant recipients, comprising 12 with stable function, 22 with T cell-mediated rejection, and 21 with biopsy-proven BKPyVAN. Our findings reveal that the ddcfmtDNA-to-ddcfDNA ratio exhibits superior capability in distinguishing BKPyVAN from other conditions, with a cutoff value of 4.96% (area under curve = 0.933; sensitivity: 71.4%; and specificity: 97.1%). Notably, an elevation of ddcfmtDNA levels is associated with mitochondrial damage, as visualized through electron microscopy. These results underscore the promise of non-invasive monitoring for detecting subtle mitochondrial damage and its potential utility in BKPyVAN diagnosis. Further investigations are required to advance this field of research.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Transplante de Rim/efeitos adversos , Vírus BK/genética , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/patologia , Rejeição de Enxerto , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/patologia , Mitocôndrias/genética , DNA Mitocondrial/genética
13.
Cell Death Dis ; 15(1): 75, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242872

RESUMO

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.


Assuntos
Rejeição de Enxerto , Fatores de Transcrição NFATC , Neutrófilos , Ratos , Animais , Trogocitose , Macrófagos
14.
Mol Pharm ; 21(2): 373-392, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38252032

RESUMO

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Qualidade de Vida , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular
15.
Clin Rheumatol ; 43(1): 315-324, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37642763

RESUMO

INTRODUCTION: IgG4-related disease (IgG4-RD) is a multiorgan autoimmune disorder that causes irreversible injury. Deteriorated kidney functions are common but easily ignored complications associated with IgG4-RD. Yet the clinical manifestations and prognosis of this specific entity have not been fully illustrated. METHOD: Three hundred fifty patients with IgG4-RD were retrospectively enrolled and divided into 119 IgG4-RD with chronic kidney disease (IgG4-RD CKD+) and 231 IgG4-RD without CKD (IgG4-RD CKD-). Demographic clinical and laboratory characteristics and survival of two cohorts were compared using restricted cubic splines, logistic and Cox regression, and Kaplan-Meier analysis. A nomogram was generated for calculating the probability of CKD in IgG4-RD. RESULTS: The spectrum of organ involvement was different between IgG4-RD CKD+ and CKD- cohorts (p<0.001). Lung (26.89%) and retroperitoneum (18.49%) involvement were more common in the IgG4-RD CKD+ cohort. Increased serum potassium and phosphorus, reduced calcium levels, and hypocomplementemia (all p<0.05) were observed in IgG4-RD CKD+. Restricted cubic splines revealed a U-shaped plot regarding associations between serum potassium and CKD. Kaplan-Meier analysis demonstrated significantly lower long-term survival rates in IgG4-RD patients with kidney function at CKD stages 4-5. Cox regression revealed declined kidney functions (G4 HR 6.537 (95% CI: 1.134-37.675)) associated with increased all-cause mortality in IgG4-RD patients. A nomogram was constructed to predict CKD in IgG4-RD promptly with a discrimination (C-index) of 0.846. CONCLUSIONS: CKD in IgG4-RD was associated with poor outcomes and electrolyte disturbances. Patients with IgG4-RD should be aware of possible deterioration in kidney function. The nomogram proposed would help to identify the subtle possibility of CKD in IgG4-RD. Key points • IgG4-related diseases with deteriorated kidney function have specific clinical and laboratory characteristics. • It is crucial to recognize and address the negative impact of deteriorating kidney function in IgG4-related diseases to prevent further harm. • The nomogram proposed would help to identify subtle kidney involvement by evaluating the possibility of CKD in IgG4-related diseases.


Assuntos
Doenças Autoimunes , Doença Relacionada a Imunoglobulina G4 , Insuficiência Renal Crônica , Humanos , Doença Relacionada a Imunoglobulina G4/complicações , Estudos Retrospectivos , Prognóstico , Insuficiência Renal Crônica/complicações , Fenótipo , Rim , Potássio
16.
Free Radic Biol Med ; 212: 295-308, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38141890

RESUMO

Schistosomiasis, caused by Schistosoma spp., is a zoonotic parasitic disease affecting human health. Rattus norvegicus (rats) are a non-permissive host of Schistosoma, in which the worms cannot mature and cause typical egg granuloma. We previously demonstrated that inherent high levels of nitric oxide (NO), produced by inducible NO synthase (iNOS), is a key molecule in blocking the development of S. japonicum in rats. To further explore the mechanism of NO inhibiting S. japonicum development in rats, we performed S-nitrosocysteine proteomics of S. japonicum collected from infected rats and mice. The results suggested that S. japonicum in rats may have undergone endoplasmic reticulum (ER) stress. Interestingly, we found that the ER of S. japonicum in rats showed marked damage, while the ER of the worm in iNOS-/- rats and mice were relatively normal. Moreover, the expression of ER stress markers in S. japonicum from WT rats was significantly increased, compared with S. japonicum from iNOS-/- rats and mice. Using the NO donor sodium nitroprusside in vitro, we demonstrated that NO could induce ER stress in S. japonicum in a dose-dependent manner, and the NO-induced ER stress in S. japonicum could be inhibited by ER stress inhibitor 4-Phenyl butyric acid. We further verified that inhibiting ER stress of S. japonicum in rats promoted parasite development and survival. Furthermore, we demonstrated that NO-induced ER stress of S. japonicum was related to the efflux of Ca2+ from ER and the impairment of mitochondrial function. Collectively, these findings show that high levels of NO in rats could induce ER stress in S. japonicum by promoting the efflux of Ca2+ from ER and damaging the mitochondrial function, which block the worm development. Thus, this study further clarifies the mechanism of anti-schistosome in rats and provides potential strategies for drug development against schistosomiasis and other parasitosis.


Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Ratos , Camundongos , Humanos , Animais , Óxido Nítrico , Mitocôndrias , Estresse do Retículo Endoplasmático , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/parasitologia
17.
Neuropsychiatr Dis Treat ; 19: 2709-2728, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077240

RESUMO

Background: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability and is up-regulated during axonal regeneration. Here, serum SPARCL1 was determined for estimating severity and prognosticating early neurological deterioration (END) and functional outcomes of acute intracerebral hemorrhage (ICH). Methods: In this prospective observational cohort study of 156 patients with supratentorial ICH, blood samples of 53 were acquired not only at admission but also ad days 1, 3, 5, 7 and 10. Another group of 53 healthy controls were recruited. The modified Rankin Scale (mRS) scores of 3-6 at poststroke six months were regarded as poor prognosis. Results: As opposed to controls, serum SPARCL1 levels were markedly elevated during the early ten days after ICH, with the highest levels at days 1 and 3. Admission serum SPARCL1 levels were independently correlated with National Institutes of Health Stroke Scale scores and hematoma volume, were significantly increased in the order of six-month mRS scores from 0 to 6 and were independently correlated with six-month mRS scores. Serum SPARCL1 levels were linearly related to risks of poor six-month prognosis and END under restricted cubic spline, had significant efficiency under receiver operating characteristic (ROC) curve and were independently associated with END and poor prognosis. Subgroup analysis confirmed that no interactions existed for associations of serum SPARCL1 levels with other variables, such as age, gender and some specific vascular risk factors. END and poor prognosis prediction models integrating serum SPARCL1 were displayed using the two nomograms. The poor prognosis prediction model, but END prediction model not, performed well under calibration curve, decision curve and ROC curve. Conclusion: A substantial elevation of serum SPARCL1 levels during the early period after ICH is independently related to illness severity and poor neurological outcomes, thus signifying that serum SPARCL1 may appear as a prognostic biomarker of ICH.

18.
BMC Infect Dis ; 23(1): 888, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114917

RESUMO

BACKGROUND: Lymphomas involving the gastrointestinal tract may be manifested as anti-inflammatory tract bleeding, abdominal lymph node enlargement, or even perforation of the gastrointestinal tract. After organ transplantation, the likelihood of post-transplant lymphoproliferative disorders increases, and some rare infections may also appear. CASE PRESENTATION: Herein, we report a living transplant patient with talaromycosis marneffei (TSM) or Talaromyces marneffei (TM) infection with gastrointestinal hemorrhage and systemic lymph node enlargement, which presented clinically as lymphoma. CONCLUSION: This case is TSM in a kidney transplant patient, confirmed by lymph node biopsy and blood culture. The patient discharged from hospital successfully under the treatment of antifungal therapy and immunosuppressive therapy. Physicians should be aware that TSM can mimic lymphoma, and early diagnosis and treatment can benefit the outcomes.


Assuntos
Transplante de Rim , Linfadenopatia , Linfoma , Humanos , Antifúngicos/uso terapêutico , Transplante de Rim/efeitos adversos , Diagnóstico Diferencial , Linfoma/diagnóstico , Linfadenopatia/tratamento farmacológico
19.
Cancers (Basel) ; 15(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38136381

RESUMO

Glioblastoma (GBM) represents a paramount challenge as the most formidable primary brain tumor characterized by its rapid growth, aggressive invasiveness, and remarkable heterogeneity, collectively impeding effective therapeutic interventions. The cancer stem cells within GBM, GBM stem cells (GSCs), hold pivotal significance in fueling tumor advancement, therapeutic refractoriness, and relapse. Given their unique attributes encompassing self-renewal, multipotent differentiation potential, and intricate interplay with the tumor microenvironment, targeting GSCs emerges as a critical strategy for innovative GBM treatments. Natural killer (NK) cells, innate immune effectors recognized for their capacity to selectively detect and eliminate malignancies without the need for prior sensitization, offer substantial therapeutic potential. Harnessing the inherent capabilities of NK cells can not only directly engage tumor cells but also augment broader immune responses. Encouraging outcomes from clinical investigations underscore NK cells as a potentially effective modality for cancer therapy. Consequently, NK cell-based approaches hold promise for effectively targeting GSCs, thereby presenting an avenue to enhance treatment outcomes for GBM patients. This review outlines GBM's intricate landscape, therapeutic challenges, GSC-related dynamics, and elucidates the potential of NK cell as an immunotherapeutic strategy directed towards GSCs.

20.
Phys Chem Chem Phys ; 25(45): 31206-31221, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37955184

RESUMO

The biological characteristics of planar heterojunction nanomaterials and their interactions with biomolecules are crucial for the potential application of these materials in the biomedical field. This study employed molecular dynamics (MD) simulations to investigate the interactions between proteins with distinct secondary structures (a single α-helix representing the minimal oligomeric domain protein, a single ß-sheet representing the WW structural domain of the Yap65 protein, and a mixed α/ß structure representing the BBA protein) and a planar two-dimensional heterojunction (a GRA/h-BN heterojunction consisting of a graphene nanoplate (GRA) and a hexagonal boron nitride nanoplate (h-BN)). The results indicate that all three kinds of protein can be quickly and stably adsorbed on the GRA/h-BN heterojunction due to the strong van der Waals interaction, regardless of their respective types, structures and initial orientations. Moreover, the proteins exhibit a pronounced binding preference for the hBN region of the GRA/h-BN heterojunction. Upon adsorption, the α-helix structure of the minimal oligomeric domain protein experiences partial or complete denaturation. Conversely, while the secondary structure of the single ß-sheet and mixed α/ß structure (BBA protein) undergoes slight changes (focus on the coil and turn regions), the main α-helix and ß-sheet structures remain intact. The initial orientation significantly impacts the degree of protein adsorption and its position on the GRA/h-BN heterojunction. However, regardless of the initial orientation, proteins can ultimately be adsorbed onto the GRA/h-BN heterojunction. Furthermore, the initial orientation has a minor influence on the structural changes of proteins. Significantly, the combination of different secondary structures helps mitigate the denaturation of a single α-helix structure to some extent. Overall, the adsorption of proteins on GRA/h-BN is primarily driven by van der Waals and hydrophobic interactions. Proteins with ß-sheet or mixed structures exhibit stronger biocompatibility on the GRA/h-BN heterojunction. Our research elucidated the biological characteristics of GRA/h-BN heterojunction nanomaterials and their interactions with proteins possessing diverse secondary structures. It offers a theoretical foundation for considering heterojunction nanomaterials as promising candidates for biomedical applications.


Assuntos
Grafite , Grafite/química , Adsorção , Simulação de Dinâmica Molecular , Compostos de Boro/química
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