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1.
Front Plant Sci ; 15: 1487639, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39439513

RESUMEN

Maize is one of the most successful crops in utilizing heterosis which significantly improves maize stresses resistance and yield. Drought is a destructive abiotic stress that significantly reduces crop yield, particularly in maize. Drought stress and re-watering frequently occur during the growth and development of maize; however, the molecular mechanisms of heterosis under drought stress and re-watering have rarely been systematically investigated. Zhengdan7137 and Zhengdan7153 are two maize hybrid varieties with robust heterosis, and separately belongs to the SS×NSS and Reid×Tangsipingtou heterotic groups. 54 transcriptomes of these two hybrids and their parental inbred lines were analyzed under well-watering (WW), water-deficit (WD), and re-watering (RW) conditions using RNA-Seq. In this study, we identified 3,411 conserved drought response genes (CDRGs) and 3,133 conserved re-watering response genes (CRRGs) between Zhengdan7137 and Zhengdan7153. When comparing CDRGs and CRRGs to overdominance and underdominance genes, we identified 303 and 252 conservative drought response overdominance genes (DODGs) and underdominance genes (DUDGs), respectively, and 165 and 267 conservative re-watering response overdominance genes (RODGs) and underdominance genes (RUDGs), respectively. DODGs are involved in stress response-related processes, such as L-phenylalanine metabolism, carbohydrate metabolism, and heat response, whereas DUDGs are associated with glucose metabolism, pentose-phosphate shunt, and starch metabolism. RODGs and RUDGs contribute to the recovery of hybrids from drought stress by upregulating cell propagation and photosynthesis processes, and repressing stress response processes, respectively. It indicated overdominant and underdominant genes conservatively contributed to hybrid heterosis under drought stress. These results deepen our understanding of the molecular mechanisms of drought resistance, uncover conservative molecular mechanisms of heterosis under drought stress and re-watering, and provide potential targets for improving drought resistance in maize.

2.
Bioact Mater ; 42: 226-240, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39285915

RESUMEN

Hematopoietic stem cell transplantation (HSCT) is extensively employed in the treatment of hematological malignancies but is markedly constrained by the paucity of hematopoietic stem/progenitor cells (HSPCs). Recent studies have found that marrow adipose tissue (MAT) acts on hematopoiesis through complicated mechanisms. Therefore, the osteo-organoids fabricated in vivo using biomaterials loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) have been used as models of MAT for our research. To obtain sufficient amounts of therapeutic HSPCs and healthy MAT, we have developed amphiphilic chitosan (AC)-gelatin as carriers of rhBMP-2 to the regulate type conversion of adipose tissue and trap hematopoietic growth factors. Unlike medicine interventions or cell therapies, the traps based on AC not only attenuate the occupancy of adipocytes within the hematopoietic microenvironment while preserving stem cell factor concentrations, but also improve marrow metabolism by promoting MAT browning. In conclusion, this approach increases the proportion of HSPCs in osteo-organoids, and optimizes the composition and metabolic status of MAT. These findings furnish an experimental basis for regulating hematopoiesis in vivo through materials that promote the development of autologous HSPCs. Additionally, this approach presents a theoretical model of rapid adipogenesis for the study of adipose-related pathologies and potential pharmacological targets.

3.
J Neurol ; 271(10): 6811-6821, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39190107

RESUMEN

OBJECTIVE: The overlapping syndrome of anti-GFAP and anti-MOG antibodies is extremely rare. This retrospective study reports 8 adult cases of the GFAP-MOG overlapping syndrome. METHODS: We reviewed the clinical characteristics of 8 adult patients with the GFAP-MOG overlapping syndrome from Jan 2019 and Sep 2023 at the Third Affiliated Hospital, Sun Yat-sen University. Moreover, we searched the literature and included all case reports with this overlapping syndrome since 2018 on PubMed. RESULTS: The predominant clinical syndrome was meningoencephalomyelitis (5/8), followed by meningoencephalitis (2/8), and myelitis (1/8). Five patients had a flu-like prodromal symptom or diarrhea. No neoplasms were found in these patients. Regarding brain MRI, T2-weighted/fluid-attenuated inversion recovery hyperintensities were in 7 patients and leptomeningeal enhancement was in 4 patients. However, only one patient had periventricular radial linear enhancement. Besides, two patients had large space-occupying lesions. For spinal MRI, T2-hyperintensities were observed in 4 patients, in which 3 patients had longitudinally extensive lesions. All patients were treated with immunotherapy, the median follow-up period was 18 months (range, 3-36 months). Three patients presented relapses during the follow-up, but all cases recovered to mRS scores ≤ 2 at last follow-up. In addition, we also reviewed 14 cases (including 7 adults and 7 children) with this overlapping syndrome by literature review. CONCLUSION: Our findings provide data to understand the clinical features and prognosis of the GFAP-MOG overlapping syndrome. Recognizing this overlapping syndrome will expand our knowledge, allowing for better management of these patients.


Asunto(s)
Autoanticuerpos , Proteína Ácida Fibrilar de la Glía , Glicoproteína Mielina-Oligodendrócito , Humanos , Masculino , Femenino , Adulto , Proteína Ácida Fibrilar de la Glía/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Persona de Mediana Edad , Autoanticuerpos/sangre , Inmunoglobulina G/sangre , Meningoencefalitis/diagnóstico por imagen , Meningoencefalitis/inmunología , Meningoencefalitis/complicaciones , Estudios Retrospectivos , Mielitis/diagnóstico por imagen , Mielitis/inmunología , Adulto Joven , Síndrome
4.
ACS Nano ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39042820

RESUMEN

High-entropy materials (HEMs) have garnered extensive attention owing to their diverse and captivating physicochemical properties. Yet, fine-tuning morphological properties of HEMs remains a formidable challenge, constraining their potential applications. To address this, we present a rapid, low-energy consumption diethylenetriamine (DETA)-assisted microwave hydrothermal method for synthesizing a series of two-dimensional high-entropy selenides (HESes). Subsequently, the obtained HESes are harnessed for photocatalytic water splitting. Noteworthy is the optimized HESes, Cd0.9Zn1.2Mn0.4Cu1.8Cr1.2Se4.5, showcasing an output rate of hydrogen of 16.08 mmol h-1 g-1 and a quantum efficiency of ca. 30% under 420 nm monochromatic LED irradiation. It is revealed that the photocatalytic performance of these HESes stems not only from the enlarged specific surface area and enhanced photogenerated charge carrier utilization efficiency but also from the promoted formation of the Cd-Hads bond, influenced by multiple principal elements on the Cd. These findings provide a guide for the design of HEMs tailored for various applications.

5.
Med Mycol ; 62(5)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38710585

RESUMEN

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P = 0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P = 0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.


We retrospectively analyzed CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA by mNGS and compared 10-week survival rates among those with and without EBV DNA. Positive CSF-EBV DNA is associated with the increased mortality in HIV-negative CM patients.


Asunto(s)
ADN Viral , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Meningitis Criptocócica , Humanos , Meningitis Criptocócica/mortalidad , Meningitis Criptocócica/líquido cefalorraquídeo , Meningitis Criptocócica/microbiología , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , ADN Viral/líquido cefalorraquídeo , ADN Viral/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/líquido cefalorraquídeo , Anciano , Líquido Cefalorraquídeo/microbiología , Líquido Cefalorraquídeo/virología , Cryptococcus neoformans/genética , Cryptococcus neoformans/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Adulto Joven , China/epidemiología , Análisis de Supervivencia
6.
Natl Sci Rev ; 11(5): nwae076, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38577669

RESUMEN

China's aging demographic poses a challenge for treating prevalent bone diseases impacting life quality. As bone regeneration capacity diminishes with age due to cellular dysfunction and inflammation, advanced biomaterials-based approaches offer hope for aged bone regeneration. This review synthesizes materiobiology principles, focusing on biomaterials that target specific biological functions to restore tissue integrity. It covers strategies for stem cell manipulation, regulation of the inflammatory microenvironment, blood vessel regeneration, intervention in bone anabolism and catabolism, and nerve regulation. The review also explores molecular and cellular mechanisms underlying aged bone regeneration and proposes a database-driven design process for future biomaterial development. These insights may also guide therapies for other age-related conditions, contributing to the pursuit of 'healthy aging'.

7.
Mult Scler Relat Disord ; 85: 105527, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38432014

RESUMEN

OBJECTIVE: The differential diagnosis between autoimmune glial fibrillary acidic protein astrocytopathy (AGFAPA) mimicking tuberculous meningitis and tuberculous meningitis (TBM) remains challenging in clinical practice. This study aims to identify the clinical, laboratory parameters, and clinical score systems that may be helpful in differentiating AGFAPA from TBM. METHOD: Overall 22 AGFAPA patients who were initially misdiagnosed as TBM (AGFAPA-TBM) and 30 confirmed TBM patients were included. The clinical, laboratory, imaging parameters, Thwaites systems, and Lancet consensus scoring systems (LCSS) of all patients were reviewed. Logistic regression was employed to establish a diagnostic formula to differentiate AGFAPA-TBM from TBM. The receiver operating characteristic (ROC) curve was applied to determine the best diagnostic critical point of the formula. RESULTS: Urinary retention was more frequent in AGFAPA-TBM patients (72.7% vs 33.3%, p = 0.012). A significantly lower ratio of T-SPOT. TB was noted in AGFAPA-TBM patients (9.1% vs 82.1%, p < 0.001). We found the LCSS was able to differentiate AGFAPA-TBM from TBM (AUC value 0.918, 95% CI=0.897-0.924). Furthermore, we set up a new scoring system with three variables: urinary retention, T-SPOT. TB, and cerebral imaging criteria in LCSS. The proposed diagnostic score ranges from -8 to 2, and a score of ≥ 0 was suggestive of AGFAPA-TBM (AUC value 0.938, 95% CI=0.878-0.951). CONCLUSIONS: This study is the first to evaluate the Thwaites system and LCSS in AGFAPA-TBM and TBM. We provide an alternative diagnostic formula to differentiate AGFAPA-TBM from TBM and suggest testing for GFAP antibodies to avoid misdiagnosis when this scoring system meets AGFAPA-TBM.


Asunto(s)
Proteína Ácida Fibrilar de la Glía , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/diagnóstico , Femenino , Masculino , Diagnóstico Diferencial , Proteína Ácida Fibrilar de la Glía/inmunología , Adulto , Persona de Mediana Edad , Adulto Joven , Estudios Retrospectivos , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Astrocitos/inmunología , Autoanticuerpos/sangre
8.
Neurotoxicology ; 102: 1-11, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38461971

RESUMEN

Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits.


Asunto(s)
Biomarcadores , Eritrocitos , Manganeso , Síndromes de Neurotoxicidad , Animales , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Manganeso/sangre , Manganeso/toxicidad , Manganeso/orina , Biomarcadores/sangre , Biomarcadores/orina , Masculino , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/sangre , Ratas , Humanos , Intoxicación por Manganeso/sangre , Ratas Sprague-Dawley , Exposición Profesional/efectos adversos , Femenino
10.
J Vis Exp ; (204)2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38436379

RESUMEN

Hematopoietic stem cell transplantation (HSCT) requires a sufficient number of therapeutic hematopoietic stem/progenitor cells (HSPCs). To identify an adequate source of HSPCs, we developed an in vivo osteo-organoid by implanting scaffolds loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) into an internal muscle pouch near the femur in mice. After 12 weeks of implantation, we retrieved the in vivo osteo-organoids and conducted flow cytometry analysis on HPSCs, revealing a significant presence of HSPC subsets within the in vivo osteo-organoids. We then established a sublethal model of hematopoietic/immune system injury in mice through radiation and performed hematopoietic stem cell transplantation (HSCT) by injecting the extracted osteo-organoid-derived cells into the peripheral blood of radiated mice. The effect of hematopoietic recovery was evaluated through hematological, peripheral blood chimerism, and solid organ chimerism analyses. The results confirmed that in vivo osteo-organoid-derived cells can rapidly and efficiently reconstruct damaged peripheral and solid immune organs in irradiated mice. This approach holds potential as an alternative source of HSPCs for HSCT, offering benefits to a larger number of patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Recolección de Tejidos y Órganos , Humanos , Animales , Ratones , Organoides , Quimerismo , Células Madre Hematopoyéticas
11.
Cancer Med ; 13(4): e7018, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38457189

RESUMEN

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Hepatectomy remains the first-line treatment for patients with resectable HCC. However, the reported recurrence rate of HCC at 5 years after surgery is between 50% and 70%. Tumor-related factors, including tumor size, number and differentiation, and underlying liver disease are well-known risk factors for recurrence after treatment. In addition to tumor-related factors, ever-increasing amounts of studies are finding that the tumor microenvironment also plays an important role in the recurrence of HCC, including systemic inflammatory response and immune regulation. Based on this, some inflammatory and immune markers were used in predicting postoperative cancer recurrence. These include neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, cytotoxic T cells, and regulatory T cells, among others. In this review, we summarized the inflammatory and immune markers that affect recurrence after HCC resection in order to provide direction for adjuvant therapy after HCC resection and ultimately achieve the goal of reducing recurrence.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Hepatectomía/efectos adversos , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/cirugía , Inflamación/etiología , Linfocitos/patología , Biomarcadores , Estudios Retrospectivos , Pronóstico , Microambiente Tumoral
12.
Exp Hematol ; 133: 104192, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38432427

RESUMEN

Hematopoietic stem cell transplantation remains the preferred treatment for a variety of hematopoietic function disorders. To address the issue of limited numbers of hematopoietic stem/progenitor cells (HSPCs), significant progress has been made in the technology for ex vivo expansion of HSPCs. In addition, biomaterial-assisted in vivo production technology for therapeutic cells, including HSPCs, is gradually gaining attention. With the aid of specifically functional biomaterials, researchers can construct bone-like tissues exhibiting typical bone marrow-like structures (termed in vivo osteo-organoids in this article) for the production of therapeutic cells. These in vivo osteo-organoids mimic the native bone marrow niche and provide a microenvironment conducive to the expansion and differentiation of HSPCs. In this perspective article, we systematically summarize the history of in vivo osteo-organoids as a model for studying hematopoiesis and cancer metastasis and propose the challenges faced by the in vivo osteo-organoid production platform for therapeutic cells in terms of clinical translation. Ultimately, we hope to achieve functional customization of in vivo osteo-organoid-derived cells through continuously developed material design methods, so as to meet the treatment needs of different types of diseases and bring hope for life to more people.


Asunto(s)
Materiales Biocompatibles , Células Madre Hematopoyéticas , Humanos , Animales , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Trasplante de Células Madre Hematopoyéticas , Organoides/citología , Hematopoyesis , Diferenciación Celular
13.
Anal Chem ; 96(6): 2711-2718, 2024 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-38301229

RESUMEN

Excessive sulfite usage in food and pharmaceutical production causes respiratory and neurological diseases, underscoring the need for a sensitive and rapid quantification strategy. The portable sensing platform based on a luminescent hydrogel sensor is a powerful tool for the on-site, real-time detection of sulfite ions. However, the lack of recyclability in almost all reaction-based hydrogel sensors increases the application cost. This study constructed a reversible and upconversion nanoprobe combining upconversion nanoparticles (UCNPs) and pararosaniline (PAR) for sulfite detection. The upconversion nanoprobe was further encapsulated in a three-dimensional polyacrylamide hydrogel matrix to create a background-free, reversible hydrogel sensor. The near-infrared excitation of UCNPs avoids the autofluorescence in the hydrogel and real samples. Meanwhile, PAR serves as a specific recognition unit for sulfite ions. After the addition of sulfites, a specific reaction occurs between PAR and sulfites, leading to the recovery of characteristic emission at 540 nm, achieving sensitive detection of sulfite ions. Importantly, this specific reaction is reversible under thermal treatment, allowing the hydrogel sensor to return to its initial state and thus enabling reversible detection of sulfite ions. Furthermore, a portable sensing platform is developed to realize point-of-care, real-time quantitative detection of sulfite ions. The proposed upconversion reversible hydrogel sensor provides a new sensing strategy for the detection of hazardous substances in food and offers new insights into the preparation of reversible, highly sensitive hydrogel sensors.


Asunto(s)
Hidrogeles , Nanopartículas , Colorantes de Rosanilina , Toluidinas , Alimentos , Luminiscencia , Sulfitos
14.
J Glob Antimicrob Resist ; 36: 167-174, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38141953

RESUMEN

OBJECTIVES: The relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood. METHODS: We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year. RESULTS: All of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality. CONCLUSION: Most Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.


Asunto(s)
Criptococosis , Cryptococcus neoformans , Infecciones por VIH , Meningitis Criptocócica , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/complicaciones , Meningitis Criptocócica/microbiología , Estudios Retrospectivos , Fluconazol/farmacología , Criptococosis/complicaciones , Criptococosis/tratamiento farmacológico , Criptococosis/microbiología , Anfotericina B/farmacología , Flucitosina/farmacología , Voriconazol/farmacología , Voriconazol/uso terapéutico , Itraconazol/farmacología , Infecciones por VIH/tratamiento farmacológico
15.
Mol Immunol ; 165: 42-54, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38150981

RESUMEN

OBJECTIVE: Cells can produce stress granules (SGs) to protect itself from damage under stress. The cGAS-STING pathway is one of the important pattern recognition pathways in the natural immune system. This study was investigated whether human mesenchymal stem cells (hMSCs) could protect the liver by inducing M2 macrophages to produce SGs during acute drug induced liver injury (DILI) induced by acetaminophen (APAP). METHODS: After intragastric administration of APAP in vivo to induce DILI mice model, hMSCs were injected into the tail vein. The co-culture system of hMSCs and M2 macrophages was established in vitro. It was further use SGs inhibitor anisomicin to intervene M2 macrophages. The liver histopathology, liver function, reactive oxygen species (ROS) level, apoptosis pathway, endoplasmic reticulum stress (ERS) level, SGs markers (G3BP1/TIA-1), cGAS-STING pathway, TNF-α, IL-6, IL-1ß mRNA levels in liver tissue and M2 macrophages were observed. RESULTS: In vivo experiments, it showed that hMSCs could alleviate liver injury, inhibite the level of ROS, apoptosis and ERS, protect liver function in DILI mice. The mount of M2 was increased in the liver. hMSCs could also induce the production of SGs, inhibit the cGAS-STING pathway and reduce TNF-α, IL-6, IL-1ß mRNA expression. The results in vitro showed that hMSCs could induce the production of SGs in macrophages, inhibit the cGAS-STING pathway, promote the secretion of IL-4 and IL-13, and reduce TNF-α, IL-6, IL-1ß mRNA level in cells. In the process of IL-4 inducing M2 macrophage activation, anisomycin could inhibit the production of SGs, activate the cGAS-STING pathway, and promote the inflammatory factor TNF-α, IL-6, IL-1ß mRNA expression in cells. CONCLUSIONS: HMSCs had a protective effect on acute DILI in mice induced by APAP. Its mechanism might involve in activating M2 type macrophages, promoting the production of SGs, inhibiting the cGAS-STING pathway, and reducing the expression of pro-inflammatory factors in macrophages, to reduce hepatocytes damage.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Células Madre Mesenquimatosas , Humanos , Ratones , Animales , Factor de Necrosis Tumoral alfa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Acetaminofén/toxicidad , Acetaminofén/metabolismo , Interleucina-6/metabolismo , ADN Helicasas/metabolismo , Interleucina-4/metabolismo , Gránulos de Estrés , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Macrófagos/metabolismo , Nucleotidiltransferasas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , ARN Mensajero/metabolismo , Células Madre Mesenquimatosas/metabolismo
16.
Proc Natl Acad Sci U S A ; 120(46): e2307480120, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37943835

RESUMEN

Ischemic diseases lead to considerable morbidity and mortality, yet conventional clinical treatment strategies for therapeutic angiogenesis fall short of being impactful. Despite the potential of biomaterials to deliver pro-angiogenic molecules at the infarct site to induce angiogenesis, their efficacy has been impeded by aberrant vascular activation and off-target circulation. Here, we present a semisynthetic low-molecular sulfated chitosan oligosaccharide (SCOS) that efficiently induces therapeutic arteriogenesis with a spontaneous generation of collateral circulation and blood reperfusion in rodent models of hind limb ischemia and myocardial infarction. SCOS elicits anti-inflammatory macrophages' (Mφs') differentiation into perivascular Mφs, which in turn directs artery formation via a cell-to-cell communication rather than secretory factor regulation. SCOS-mediated arteriogenesis requires a canonical Notch signaling pathway in Mφs via the glycosylation of protein O-glucosyltransferases 2, which results in promoting arterial differentiation and tissue repair in ischemia. Thus, this highly bioactive oligosaccharide can be harnessed to direct efficiently therapeutic arteriogenesis and perfusion for the treatment of ischemic diseases.


Asunto(s)
Neovascularización Fisiológica , Sulfatos , Ratones , Animales , Neovascularización Fisiológica/fisiología , Sulfatos/metabolismo , Ratones Noqueados , Músculo Esquelético/metabolismo , Isquemia/metabolismo , Macrófagos/metabolismo , Miembro Posterior/irrigación sanguínea , Modelos Animales de Enfermedad
17.
Med Mycol ; 61(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38031335

RESUMEN

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P = .012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP < 250-mm H2O, 60.0% vs. 32.4%, P = .001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P < .001), higher baseline CSF white blood cell (median, 130 vs. 90, P = .029) and CSF protein (median, 0.87 vs. 0.73, P = .011). Multivariate analysis showed that baseline CSF OP <250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P = .019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P < .001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P < .001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP < 250-mm H2O were prone to the low-risk status.


This was a retrospective cohort study to find the features of low-risk non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM). We found that non-HIV-associated CM patients with baseline cerebrospinal fluid opening pressure <250-mm H2O were prone to low-risk status.


Asunto(s)
Cryptococcus , Infecciones por VIH , Meningitis Criptocócica , Humanos , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/líquido cefalorraquídeo , Meningitis Criptocócica/veterinaria , Estudios Retrospectivos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/veterinaria , Resultado del Tratamiento
18.
Eur Neurol ; 86(6): 363-376, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37848007

RESUMEN

INTRODUCTION: Many clinical studies reported the coexistence of Alzheimer's disease (AD) and multiple sclerosis (MS), but the common molecular signature between AD and MS remains elusive. The purpose of our study was to explore the genetic linkage between AD and MS through bioinformatic analysis, providing new insights into the shared signatures and possible pathogenesis of two diseases. METHODS: The common differentially expressed genes (DEGs) were determined between AD and MS from datasets obtained from Gene Expression Omnibus (GEO) database. Further, functional and pathway enrichment analysis, protein-protein interaction network construction, and identification of hub genes were carried out. The expression level of hub genes was validated in two other external AD and MS datasets. Transcription factor (TF)-gene interactions and gene-miRNA interactions were performed in NetworkAnalyst. Finally, receiver operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of hub genes. RESULTS: A total of 75 common DEGs were identified between AD and MS. Functional and pathway enrichment analysis emphasized the importance of exocytosis and synaptic vesicle cycle, respectively. Six significant hub genes, including CCL2, CD44, GFAP, NEFM, STXBP1, and TCEAL6, were identified and verified as common hub genes shared by AD and MS. FOXC1 and hsa-mir-16-5p are the most common TF and miRNA in regulating hub genes, respectively. In the ROC curve analysis, all hub genes showed good efficiency in helping distinguish patients from controls. CONCLUSION: Our study first identified a common genetic signature between AD and MS, paving the road for investigating shared mechanism of AD and MS.


Asunto(s)
Enfermedad de Alzheimer , MicroARNs , Esclerosis Múltiple , Humanos , Enfermedad de Alzheimer/genética , Esclerosis Múltiple/genética , MicroARNs/genética , Biología Computacional , Bases de Datos Factuales
19.
Mycoses ; 66(11): 1003-1011, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37563970

RESUMEN

OBJECTIVE: Information about the seasonal characteristics of human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) is quite limited. The aim of this study was to explore the seasonality and meteorological factors of HIV-negative patients with CM. METHODS: We performed a retrospective study of 469 HIV-negative CM patients admitted to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. Their initial onset symptoms of CM occurred from January 2011 to December 2020. The temperature, precipitation, sunlight, humidity and wind speed for the corresponding period and the associated topographic, ecological type and soil type parameters data were collected. The Poisson regression model was used to determine the meteorological factors associated with CM onset. The geographical detector method was used to detect other environmental factors associated with CM onset. RESULTS: CM onset did not showed a seasonal fluctuation, but was strongly associated with mean temperature (ß = .010, p = .028) and mean relative humidity (ß = -.011, p = .006). In the rainy season, only mean wind speed remained significantly associated with CM onset (ß = -.108, p = .041). In the dry season, mean temperature (ß = .014, p = .016), mean relative humidity (ß = -.016, p = .006) and hours of sunlight (ß = -.002, p = .016) were significantly associated with CM onset. Topographic, ecological type and soil type factors did not add explanatory power. CONCLUSIONS: Our findings add the knowledge about the environmental factors of HIV-negative CM. Meteorological factors, especially temperature and humidity, may be the main environmental factors affecting the onset of HIV-negative CM.


Asunto(s)
Infecciones por VIH , Meningitis Criptocócica , Humanos , Estudios Retrospectivos , Conceptos Meteorológicos , Temperatura , China/epidemiología , Suelo , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología
20.
J Phys Chem Lett ; 14(34): 7618-7625, 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37594947

RESUMEN

Re-based transition metal dichalcogenides have attracted extensive attention owing to their anisotropic structure and excellent properties in applications such as optoelectronic devices and electrocatalysis. The present study methodically investigated the evolution of specific Raman phonon mode behaviors and phase transitions in monolayer and bulk ReSe2 under high pressure. Considering the distinctive anisotropic characteristics and the vibration vectors of Re and Se atoms exhibited by monolayer ReSe2, we perform phonon dispersion calculations and propose a methodology utilizing pressure-dependent polarized Raman measurements to explore the precise structural evolution of monolayer ReSe2 under the stress fields. Varied behaviors of the Eg-like and Ag-like modes, along with their specific vector transformations, have been identified in the pressure range 0-14.59 GPa. The present study aims to offer original perspectives on the physical evolution of Re-based transition metal dichalcogenides, elucidating their fundamental anisotropic properties and exploring potential applicability in diverse devices.

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