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1.
J Mater Chem B ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39258439

ABSTRACT

The application of patch methods for repairing abdominal wall wounds presents a variety of challenges, such as adhesion and limited mobility due to inadequate mechanical strength and nonabsorbable materials. Among these complications, postoperative visceral adhesion and wound infection are particularly serious. In this study, a bilayered composite patch with a gelatin methacryloyl (GelMA)/sodium alginate (SA)-vancomycin (Van)@polycaprolactone (PCL) (GelMA/SA-Van@PCL) antibacterial layer was prepared via coaxial 3D printing and a polycaprolactone (PCL)-silicon dioxide (SiO2) antiadhesive layer (PCL-SiO2) was prepared via electrospinning and electrostatic spray for hernia repair. The evaluation of the physicochemical properties revealed that the composite patch had outstanding tensile properties (16 N cm-1), excellent swelling (swelling rate of 243.81 ± 12.52%) and degradation (degradation rate of 53.14 ± 3.02%) properties. Furthermore, the composite patch containing the antibiotic Van exhibited good antibacterial and long-term drug release properties. Both in vivo and in vitro experiments indicated that the composite patch displayed outstanding biocompatibility and antiadhesive properties and could prevent postoperative infections. In summary, the bilayered composite patch can effectively prevent postoperative complications while promoting tissue growth and repair and holds significant application potential in hernia repair.

2.
BMC Genomics ; 25(1): 836, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237905

ABSTRACT

BACKGROUND: The KT/HAK/KUP is the largest K+ transporter family in plants, playing crucial roles in K+ absorption, transport, and defense against environmental stress. Sweet watermelon is an economically significant horticultural crop belonging to the genus Citrullus, with a high demand for K+ during its growth process. However, a comprehensive analysis of the KT/HAK/KUP gene family in watermelon has not been reported. RESULTS: 14 KT/HAK/KUP genes were identified in the genomes of each of seven Citrullus species. These KT/HAK/KUPs in watermelon were unevenly distributed across seven chromosomes. Segmental duplication is the primary driving force behind the expansion of the KT/HAK/KUP family, subjected to purifying selection during domestication (Ka/Ks < 1), and all KT/HAK/KUPs exhibit conserved motifs and could be phylogenetically classified into four groups. The promoters of KT/HAK/KUPs contain numerous cis-regulatory elements related to plant growth and development, phytohormone response, and stress response. Under K+ deficiency, the growth of watermelon seedlings was significantly inhibited, with cultivated watermelon experiencing greater impacts (canopy width, redox enzyme activity) compared to the wild type. All KT/HAK/KUPs in C. lanatus and C. amarus exhibit specific expression responses to K+-deficiency and drought stress by qRT-PCR. Notably, ClG42_07g0120700/CaPI482276_07g014010 were predominantly expressed in roots and were further induced by K+-deficiency and drought stress. Additionally, the K+ transport capacity of ClG42_07g0120700 under low K+ stress was confirmed by yeast functional complementation assay. CONCLUSIONS: KT/HAK/KUP genes in watermelon were systematically identified and analyzed at the pangenome level and provide a foundation for understanding the classification and functions of the KT/HAK/KUPs in watermelon plants.


Subject(s)
Citrullus , Droughts , Phylogeny , Plant Proteins , Stress, Physiological , Citrullus/genetics , Citrullus/metabolism , Citrullus/growth & development , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Potassium/metabolism , Gene Expression Regulation, Plant , Genome, Plant , Multigene Family , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Potassium Deficiency/genetics , Potassium Deficiency/metabolism , Promoter Regions, Genetic
3.
Curr Med Chem ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39248068

ABSTRACT

BACKGROUND: Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive. AIM: The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development. OBJECTIVE: The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma. METHODS: This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape. RESULTS: The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma. CONCLUSION: The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma.

4.
Hernia ; 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39287831

ABSTRACT

PURPOSE: This study aimed to develop, validate, and evaluate machine learning (ML) algorithms for predicting Surgical site infections (SSI) and surgical site occurrences (SSO) after elective open inguinal hernia surgery. METHODS: A cohort of 491 patients who underwent elective open inguinal hernia surgery at Fudan University Affiliated Huadong Hospital between December 2019 and December 2020 was enrolled. To create a strong prediction model, we employed five ML methods: generalized linear model, random forest (RF), support vector machines, neural network, and gradient boosting machine. Based on the best performing model, we devised online calculators to facilitate clinicians' access to a linear predictor for patients. The receiver operating characteristic curve was utilized to evaluate the model's discriminatory capability and predictive accuracy. RESULTS: The incidence rates of SSI and SSO were 4.68% and 13.44%, respectively. Four variables (diabetes, recurrence, antibiotic prophylaxis, and duration of surgery) were identified for SSI prediction, while four variables (diabetes, size of hernias, albumin levels, and antibiotic prophylaxis) were included for SSO prediction. In the test set, the RF model showed the best predictive ability (SSI: area under the curve (AUC) = 0.849, sensitivity = 0.769, specificity = 0.769, and accuracy = 0.769; SSO: AUC = 0.740, sensitivity = 0.513, specificity = 0.821, and accuracy = 0.667). Online calculators have been developed to assess patients' risk of SSI ( https://wuqian17.shinyapps.io/predictionSSI/ ) and SSO ( https://wuqian17.shinyapps.io/predictionSSO/ ) after surgery. CONCLUSIONS: This study developed a prediction model for SSI/SSO using ML methods. It holds the potential to facilitate the selection of appropriate treatment options following elective open inguinal hernia surgery.

5.
Article in Chinese | MEDLINE | ID: mdl-39198952

ABSTRACT

Objective To explore the risk factors for the returning of pediatric liver transplant recipients to the intensive care unit (ICU) and provide reference for the clinical decision-making after surgery. Methods A retrospective analysis was conducted with the information of all the pediatric patients who underwent liver transplantation in Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine and were returned to the ICU from 2019 to 2021.The patients returned to the ICU during hospitalization and the reasons for the return were recorded.Each patient of ICU return was matched with three pediatric patients who did not return to the ICU during hospitalization.The basic information,the vital signs and laboratory indicators on the day of transfer from ICU,immunosuppressants and drug concentrations were compared between the two groups.Multivariate Logistic regression analysis was performed to explore the risk factors for the returning of pediatric liver transplant recipients to the ICU. Results The returning rate of pediatric liver transplant recipients to the ICU was 4.36%,and it was 16.00% within 48 h.The main reasons for the return included respiratory complications,abdominal infections,and hepatic vascular occlusion.Multivariate Logistic regression analysis showed that post-operative red blood cell transfusion (OR=4.554,95%CI=1.743-11.901,P=0.002) and high serum level of uric acid (OR=1.005,95%CI=1.001-1.009,P=0.014) were the risk factors for returning to the ICU.High diastolic blood pressure (OR=0.922,95%CI=0.885-0.960,P<0.001) and high total protein level (OR=0.937,95%CI=0.891-0.986,P=0.012) were the protective factors for returning to the ICU. Conclusion Post-operative red blood cell transfusion and high serum level of uric acid are independent risk factors for the returning of pediatric liver transplant recipients to the ICU.

6.
Front Genet ; 15: 1372164, 2024.
Article in English | MEDLINE | ID: mdl-39165753

ABSTRACT

Background: Preeclampsia (PE) is a global pregnancy concern, characterized by hypertension with an unclear etiology. This study employs Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to clarify its genetic and molecular roots, offering insights into diagnosis and treatment avenues. Methods: We integrated PE-specific genome-wide association study (GWAS) data, expression and protein quantitative trait loci (eQTL and pQTL) data, and single-cell data from peripheral blood mononuclear cells (PBMCs). We identified highly variable genes using single-cell information and employed MR to determine potential causality. We also combined pQTL and GWAS data, discerned genes positively associated with PE through scRNA-seq, and leveraged the Enrichr platform to unearth drug-gene interactions. Results: Our scRNA-seq pinpointed notable cell type distribution variances, especially in T helper cells (Th cells), between PE and control groups. We unveiled 591 highly variable genes and 6 directly PE-associated genes. Although MR revealed correlations with PE risk, pQTL analysis was inconclusive due to data constraints. Using DSigDB, 93 potential therapeutic agents, like Retinoic acid targeting core genes (IFITM3, NINJ1, COTL1, CD69, and YWHAZ), emerged as prospective multi-target treatments. Conclusion: Utilizing MR and scRNA-seq, this study underscores significant cellular disparities, particularly in Th cells, and identifies crucial genes related to PE. Despite some limitations, these genes have been revealed in PE's underlying mechanism. Potential therapeutic agents, such as Retinoic acid, suggest promising treatment pathways.

7.
Immunity ; 57(9): 2030-2042.e8, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39116878

ABSTRACT

Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.


Subject(s)
Hemodynamics , Hypertension , Microglia , Paraventricular Hypothalamic Nucleus , Sympathetic Nervous System , Paraventricular Hypothalamic Nucleus/metabolism , Animals , Microglia/metabolism , Hypertension/physiopathology , Mice , Sympathetic Nervous System/physiopathology , Male , Mice, Inbred C57BL , Adenosine Triphosphate/metabolism , Receptors, Purinergic P2Y12/metabolism , Inflammation/immunology , Blood Pressure , Neurons/metabolism
8.
Front Endocrinol (Lausanne) ; 15: 1419913, 2024.
Article in English | MEDLINE | ID: mdl-39104813

ABSTRACT

Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations.


Subject(s)
Hypothalamo-Hypophyseal System , Thyroid Gland , Thyroid Neoplasms , Humans , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Hypothalamo-Hypophyseal System/metabolism , Thyroid Gland/metabolism , Thyroid Hormones/metabolism , Animals , Insulin-Like Growth Factor I/metabolism
9.
Transl Psychiatry ; 14(1): 325, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107319

ABSTRACT

Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.


Subject(s)
Autism Spectrum Disorder , Disease Models, Animal , Interneurons , Parvalbumins , Prefrontal Cortex , Social Cognition , Autism Spectrum Disorder/physiopathology , Animals , Prefrontal Cortex/physiopathology , Prefrontal Cortex/metabolism , Mice , Interneurons/metabolism , Interneurons/physiology , Parvalbumins/metabolism , Male , Behavior, Animal/physiology , Social Behavior , Mice, Inbred C57BL , Female
10.
Zhongguo Fei Ai Za Zhi ; 27(7): 535-540, 2024 Jul 20.
Article in Chinese | MEDLINE | ID: mdl-39147708

ABSTRACT

The best treatment for non-small cell lung cancer is early surgical treatment, but most lung cancer is diagnosed at an advanced stage. The main treatment methods are drug and radiotherapy. However, drug resistance or no signifi cant effect of the above treatment methods is inevitable. Therefore, more methods are urgently needed for the treatment of lung cancer. Studies have confirmed that engineered exosomes have good clinical application potential in cardiovascular diseases, tumors, tissue regeneration and repair. This paper summarizes the application of engineered exosomes in the treatment of lung cancer at home and abroad.
.


Subject(s)
Exosomes , Lung Neoplasms , Exosomes/metabolism , Exosomes/transplantation , Humans , Lung Neoplasms/therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Animals
11.
World J Clin Oncol ; 15(8): 1102-1109, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39193155

ABSTRACT

BACKGROUND: Primary vaginal cancer is rare and most vaginal tumors are metastatic, often arising from adjacent gynecologic structures. Primary vaginal cancers are also more common among postmenopausal women and most of these are squamous cell carcinomas, with adenocarcinomas being relatively rare. Vaginal bleeding is the most common clinical manifestation of vaginal adenocarcinoma. About 70% of vaginal adenocarcinomas are stage I lesions at the time of diagnosis, for which radical surgery is recommended. However, more advanced vaginal cancers are not amenable to radical surgical treatment and have poor clinical outcomes. Optimal treatments modes are still being explored. Here, we report a rare case of stage IIb primary vaginal adenocarcinoma for which an individually designed vaginal applicator for after-loading radiotherapy was used to achieve good tumor control. CASE SUMMARY: A 62-year-old woman presented to our clinic after 3 months of abnormal postmenopausal vaginal bleeding. Gynecological examination, computed tomography (CT), and positron emission tomography-CT showed a large mass (about 5 cm) on the anterior vaginal wall. Colposcopy biopsy confirmed adenocarcinoma of vaginal origin. After three cycles of carboplatin plus paclitaxel chemotherapy, the lesion partially shrunk. The patient then received external irradiation of 45 gray (gy) in 25 fractions, which further reduced the vaginal lesion, followed by after-loading radiotherapy of 30 gy in 5 fractions with an individually designed vaginal applicator. Three months later, magnetic resonance imaging showed a slight thickening of the anterior vaginal wall. CONCLUSION: Primary vaginal adenocarcinoma is rare, and prognosis is poor in most vaginal cancers of locally advanced stages, which cannot be treated with radical surgery. Better tumor control can be achieved with an individualized vaginal applicator that allows administration of a higher radical dose to the tumor area while protecting normal tissues.

12.
J Biomed Res ; 38(4): 307-321, 2024 May 29.
Article in English | MEDLINE | ID: mdl-39113127

ABSTRACT

Liquid-liquid phase separation, a novel biochemical phenomenon, has been increasingly studied for its medical applications. It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes. During transcriptional regulation, dynamic condensates are formed through interactions between transcriptional elements, such as transcription factors, coactivators, and mediators. Cancer is a disease characterized by uncontrolled cell proliferation, but the precise mechanisms underlying tumorigenesis often remain to be elucidated. Emerging evidence has linked abnormal transcriptional condensates to several diseases, especially cancer, implying that phase separation plays an important role in tumorigenesis. Condensates formed by phase separation may have an effect on gene transcription in tumors. In the present review, we focus on the correlation between phase separation and transcriptional regulation, as well as how this phenomenon contributes to cancer development.

14.
BMC Pulm Med ; 24(1): 431, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39217313

ABSTRACT

OBJECTIVE: To investigate the role of Parkin overexpression-induecd mitophagy in alleviating acute lung injury of exertional heat stroke(EHS) rats. METHODS: Eighty SD rats were divided into four groups: Control group (CON group), Control Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung Micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. Enzyme-linked immunosorbent assays(ELISA) were used to determine the levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), Tumor necrosis factor-α(TNF-α), and reactive oxygen species(ROS). The morphology of mitochondria in type II epithelial cells of lung tissue was observed using transmission electron microscopy. The apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, MFN2, PTEN-L, PTEN, p62, and microtubule associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by western blot. RESULTS: Compared with the CON group, there were more severe lung injury and more higher levels of IL-6, IL-1ß, TNF-α in EHS rats. Both of the LC3-II/LC3-I ratio and the co-localization of LC3 and Tom20 in the lung tissue of EHS rats decreased. Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly alleviated. The levels of IL-6, IL-1ß, TNF-α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying acute lung injury in rats with EHS, and activation of Parkin overexpression induced-mitophagy can alleviate acute lung injury caused by EHS.


Subject(s)
Acute Lung Injury , Heat Stroke , Lung , Mitophagy , Rats, Sprague-Dawley , Reactive Oxygen Species , Ubiquitin-Protein Ligases , Animals , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Heat Stroke/metabolism , Heat Stroke/complications , Heat Stroke/pathology , Rats , Lung/metabolism , Lung/pathology , Male , Acute Lung Injury/metabolism , Reactive Oxygen Species/metabolism , Disease Models, Animal , Protein Kinases/metabolism , Protein Kinases/genetics , Tumor Necrosis Factor-alpha/metabolism , Interleukin-1beta/metabolism , Apoptosis , Interleukin-6/metabolism , Interleukin-6/genetics , Mitochondria/metabolism , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics
15.
Biochem Biophys Res Commun ; 731: 150360, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39018970

ABSTRACT

Exercise is known to be an effective intervention for depression. NADPH has been demonstrated to have neuroprotective effects in our previous studies. This study aimed to investigate if NADPH has antidepressant effects and can mimic the effects of exercise in a chronic unpredictable stress (CUS) rat model. CUS rats underwent an 8-week swimming exercise (30 min/d, 5d/w) or were intraperitoneally administered 4 mg/kg or 8 mg/kg NADPH. The open field test (OFT), sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), and forced swimming test (FST) were used to examine the antidepressant-like behaviors of the rats. Exercise, 4 mg/kg, and 8 mg/kg NADPH similarly reduced anxiety, as demonstrated by the number of fecal pellets. Meanwhile, exercise and 8 mg/kg NADPH significantly increased locomotion activity in the OFT. Exercise, 4 mg/kg, and 8 mg/kg NADPH effectively reversed CUS-induced anhedonia in rats in the SPT. Exercise, 4 mg/kg, and 8 mg/kg NADPH had no impact on appetite of depressed rats; however, 8 mg/kg NADPH increased the rats' exploratory activity in the NSFT. Exercise, 4 mg/kg, and 8 mg/kg NADPH significantly reduced the immobility time of CUS model rats, while exercise and 8 mg/kg NADPH postponed the early CUS-induced "immobility" in the FST. These results demonstrated that NADPH has similar antidepressant-like effects to exercise in CUS-induced depression model rats and is a potential exercise-mimicking antidepressant.


Subject(s)
Antidepressive Agents , Depression , Disease Models, Animal , NADP , Physical Conditioning, Animal , Rats, Sprague-Dawley , Stress, Psychological , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Male , Stress, Psychological/drug therapy , Stress, Psychological/physiopathology , NADP/metabolism , Rats , Depression/drug therapy , Behavior, Animal/drug effects , Swimming , Chronic Disease
16.
Natl Sci Rev ; 11(6): nwae142, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38966071

ABSTRACT

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

17.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2991-3001, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041159

ABSTRACT

Neuropathic pain(NP) is difficult to be treated since it has similar phenotypes but different pathogenesis in different pathological stages. Targeted intervention of the core regulatory elements at different pathological stages of NP has become a new direction of drug research and development in recent years and provides the possibility for the treatment of NP. The Mongolian medicine Naru-3(NR-3) is effective in the treatment of sciatica and trigeminal neuralgia, the mechanisms of which remain unknown. On the basis of the previous study of the priming stage, this study established the mouse model of spinal nerve ligation(SNL) and measured the changes of pain thresholds by behavioral tests. The network analysis, Western blot, immunofluorescence assay, ELISA, and agonist/antagonist were employed to decipher the mechanism of NR-3 in the treatment of NP in the maintenance stage. The results showed that NR-3 increased the mechanical and thermal pain thresholds of SNL mice, while it had no significant effect on the basal pain threshold of normal mice. NR-3 may relieve the pain in the maintenance stage of NP by blocking the matrix metalloproteinase 2(MMP2)/interleukin-1ß(IL-1ß) pathway in the astrocytes of the dorsal root ganglion(DRG) and spinal cord. The findings have enriched the biological connotation of NR-3 in the treatment of the maintenance stage of NP and provide reference for the rational use of this medicine in clinical practice.


Subject(s)
Astrocytes , Medicine, Mongolian Traditional , Neuralgia , Animals , Neuralgia/drug therapy , Neuralgia/metabolism , Mice , Astrocytes/drug effects , Astrocytes/metabolism , Male , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Neuroinflammatory Diseases/drug therapy , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Disease Models, Animal
18.
Front Immunol ; 15: 1414573, 2024.
Article in English | MEDLINE | ID: mdl-39044832

ABSTRACT

Dedicator of cytokinesis 8 (DOCK8) deficiency represents a primary immunodeficiency with a wide range of clinical symptoms, including recurrent infections, atopy, and increased malignancy risk. This study presents a case of a 6-year-old girl with DOCK8 deficiency, characterized by severe, treatment-resistant herpetic infections who was successfully treated with siltuximab and glucocorticoids. The successful use of siltuximab in achieving remission highlights the pivotal role of interleukin-6 (IL-6) in DOCK8 deficiency pathogenesis and suggests that IL-6 modulation can be critical in managing DOCK8 deficiency-related viral infections, which may inform future therapeutic strategies for DOCK8 deficiency and similar immunodeficiencies.


Subject(s)
Guanine Nucleotide Exchange Factors , Prednisone , Humans , Female , Child , Guanine Nucleotide Exchange Factors/deficiency , Guanine Nucleotide Exchange Factors/genetics , Prednisone/therapeutic use , Warts/drug therapy , Warts/diagnosis , Treatment Outcome , Recurrence , Interleukin-6 , Antibodies, Monoclonal
19.
Updates Surg ; 2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39033484

ABSTRACT

Parastomal hernias (PSH) are difficult to manage and associated with high rates of postoperative recurrence and complications. Sugarbaker and three-dimensional (3-D) mesh repair are commonly used methods for the surgical treatment of PSH. However, the efficacy and safety of these surgical techniques have not been adequately compared. Patients with PSH who received 3-D mesh or Sugarbaker repair at our center from August 2012 to May 2023 were included. We retrospectively analyzed their demographic data and postoperative outcomes. The primary outcome measure was the recurrence rate at 1-year follow-up. A total of 86 patients were enrolled, involving 53 in the 3-D mesh (62%) group and 33 in the Sugarbaker (38%) group. Most cases (73%) involved were the laparoscopic approach. The recurrence rate at 1-year follow-up was 15% (eight cases) in the 3-D mesh group and 24% (eight cases) in the Sugarbaker group, with no statistical significance (P = 0.29). Additionally, no differences were observed between the 3-D mesh and Sugarbaker groups in the length of hospitalization or in short- and long-term complications. Sugarbaker and 3-D mesh repair have similar clinical efficacy in the surgical treatment of PSH. Further randomized controlled trials are required to confirm these results.Trial registration number.This study was retrospectively registered at clinicaltrials.gov (NCT06077318).

20.
Australas J Dermatol ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39031070

ABSTRACT

Infantile bullous pemphigoid (BP) is a rare autoantibody-mediated skin disorder. We report the effective treatment of a 6-month-old infant with BP using baricitinib, a Janus kinase (JAK) inhibitor, after failure with steroids and intravenous immunoglobulin. The patient achieved full remission and discontinued all medications without any relapses. To our knowledge, this is the first case of baricitinib used in an infant with BP.

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