Therapeutic efficacy of rituximab combined with cyclosporin A on B-cell dysregulation in chronic graft-versus-host disease.

OBJECTIVE: Chronic graft-versus-host disease (cGVHD) is a significant complication following allogenic hematopoietic stem cell transplantation, often necessitating therapeutic interventions such as rituximab (RTX) and cyclosporin A (CsA). This study aims to elucidate the mechanisms by which RTX and CsA jointly address B-cell dysregulation in cGVHD, providing a theoretical foundation and scientific rationale for the treatment and prognostic evaluation of this condition. METHODS: A total of 30 cGVHD mouse models were established by subjecting recipient mice to total body irradiation followed by injection of a mixed suspension of bone marrow cells and splenocytes from donor mice. From Day 2 to Day 29 post-model establishment, the mice received subcutaneous administration of RTX and CsA. Throughout the study, body weight, clinical cGVHD scores, and survival rates were monitored. Blood samples were collected via the orbital venous plexus. Serum levels of B-cell activating factor (BAFF) and pro-inflammatory factors were measured using enzyme-linked immunosorbent assay (ELISA), and the ratio of regulatory B cells (Bregs) in the blood sample was assessed via flow cytometry. RESULTS: Mice with cGVHD exhibited a 14.5% decrease in body weight, elevated clinical scores, and more severe symptoms compared to the control group. Notably, all mice in both the cGVHD and control groups survived until the conclusion of the study. Induction of cGVHD resulted in B-cell dysregulation, evidenced by elevated serum BAFF levels and a decreased proportion of Bregs. However, treatment with RTX combined with CsA ameliorated B-cell dysregulation and significantly reduced serum levels of pro-inflammatory factors in cGVHD mice, with decreases of 39.78% in TNF-α and 37.89% in IL-6. CONCLUSION: The combination of RTX and CsA effectively mitigates B-cell dysregulation in cGVHD, thereby reducing the severity and progression of the disease.

Soil erosion assessment in the Amazon basin in the last 60 years of deforestation.

Anthropic activities in the Amazon basin have been compromising the environmental sustainability of this complex biome. The main economic activities depend on the deforestation of the rainforest for pasture cattle ranching and agriculture. This study analyzes soil erosion to understand how deforestation has impacted the Amazon basin in this context, using three land-use temporal maps (1960, 1990, 2019) through the revised universal soil loss equation (RUSLE). Our results point to a significant influence of deforestation due to the expansion of agricultural and livestock activities on soil erosion rates in the Amazon Basin. The average soil erosion rate has increased by more than 600% between 1960 and 2019, ranging from 0.015 Mg ha-1 year-1 to 0.117 Mg ha-1 year-1. During this period, deforestation of the Amazon rainforest was approximately 7% (411,857 km2), clearly the leading cause of this increase in soil erosion, especially between 1990 and 2019. The south and southeast regions are the most impacted by increasing soil erosion, in which deforestation was accelerated for expanding agriculture and livestock activities, mainly in the sub-basins of the Madeira, Solimões, Xingu, and Tapajós that present soil erosion increases of 390%, 350%, 280%, and 240%, respectively. The sub-basins with the highest sediment delivery rate (SDR) are under the influence of the Andes, highlighting Solimões (27%), Madeira (13%), and Negro (6%) due to the increase in the soil erosion rate increase in these sub-basins.

Comparative research on morphology and mechanical property of integument of Rana dybowskii, Xenopus laevis and Ambystoma mexicanum.

Amphibians' integument is a multifunctional organ offering protection from the exterior surroundings and facilitating the physiological change of gas, water and salts with the environment, which is a natural biomaterial with multifunctional features. Interspecies comparison of biomechanical characters and microstructure possibly related to them were performed on the integument of three species of amphibians, two anurans(Rana dybowskii and Xenopus laevis) and one urodeles(Ambystoma mexicanum) using tensile testing and morphological characterization. It was found that the integument of Rana dybowskii and Xenopus laevis was covered by polygonal epidermal cells, while the trunk surface of Ambystoma mexicanum presented irregular microstructure with the lack of keratinization. The integument of Rana dybowskii and Xenopus laevis exhibited good performance on stiffness and strength, which showed quite high mean elastic modulus, 931MPa and 1048MPa,respectively.

Sudden Hypotension and Increased Serum Interferon-γ and Interleukin-10 Predict Early Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To identify clinical and laboratory predictors for early macrophage activation syndrome (MAS) associated with systemic juvenile idiopathic arthritis (sJIA). STUDY DESIGN: This is a retrospective cohort study of 149 patients with sJIA, of whom 27 had 31 episodes of MAS. We evaluated the clinical and laboratory features of patients with sJIA and MAS and compared them with those without MAS. We focused our analysis on the overall process of MAS development, especially MAS onset. RESULTS: As shown in previous studies, we found a high percentage of fever, absence of arthritis, and central nervous system dysfunction at MAS onset in our study cohort. We also found that 35% of patients with MAS had hypotension although not shock, and 22.6% of patients with MAS had gastrointestinal involvement at MAS onset. Compared with patients with MAS without hypotension, patients with MAS and hypotension had greater rates of admission to the intensive care unit; presented with more arthritis, serositis, pneumonia, and gastrointestinal involvement; and had greater white blood cell and absolute neutrophil counts and serum bilirubin levels and lower serum total protein. We confirmed laboratory markers such as platelet counts, lactate dehydrogenase, and aspartate aminotransferase can help to identify early MAS and that ferritin/erythrocyte sedimentation rate ratio of approximately 20.0 had a high diagnostic sensitivity and specificity for MAS. In addition, we discovered that the combination of interferon-γ >17.1 pg/mL and interleukin-10 >7.8 pg/mL appeared to be a good cytokine pattern for the recognition of MAS onset. CONCLUSIONS: Sudden hypotension, elevated ferritin/erythrocyte sedimentation rate ratio, and the cytokine pattern of significantly increased interferon-γ and interleukin-10 levels are important markers for early identification of MAS in addition to the traditional characteristics of sJIA-associated MAS.

Circ-PRMT5 enhances the proliferation, migration and glycolysis of hepatoma cells by targeting miR-188-5p/HK2 axis.

INTRODUCTION AND OBJECTIVES: Circular RNA (circRNA) has been demonstrated as a critical regulator in human cancer, including hepatocellular carcinoma (HCC). Nevertheless, the role of circ-PRMT5 in HCC remains largely unknown. PATIENTS OR MATERIALS AND METHODS: The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to assess the expression levels of circ-PRMT5, miR-188-5p and anti-Hexokinase II (HK2) in HCC tissues and cells. The cell proliferation, migration and glycolysis were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell migration assay, and indicated kits, respectively. The interaction relationship between miR-188-5p and circ-PRMT5 or HK2 was analyzed by the bioinformatics database, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. The western blot assay was used to analyze the expression level of HK2. The functional role of circ-PRMT5 in vivo was assessed by a xenograft experiment. RESULTS: Circ-PRMT5 was elevated in HCC tissues and cells than matched control groups. Furthermore, loss-of-functional experiments revealed that the silencing of circ-PRMT5 could repress proliferation, migration, glycolysis in vitro and tumor growth in vivo. Moreover, we also confirmed that overexpression of circ-PRMT5 abolished the effects on HCC cells induced by upregulating miR-188-5p. In addition, overexpression of miR-188-5p could repress the development of HCC. More importantly, HK2 was a target gene of miR-188-5p, and miR-188-5p regulated proliferation, migration, glycolysis of HCC cells by specifically binding to HK2. Mechanistically, circ-PRMT5 could act as a sponge of miR-188-5p to regulate the expression of HK2. CONCLUSION: In summary, circ-PRMT5 might play a key role in proliferation, migration, glycolysis of HCC cells via miR-188-5p/HK2 axis, which indicated that circ-PRMT5 might be a potential therapeutic target for HCC treatment.

Effect of FPZ, a total flavonoids ointment topical application from Pouzolzia zeylanica var. microphylla, on mice skin infections

ABSTRACT The present study was designed to investigate the effect of FPZ, a total flavonoids ointment topical application from Pouzolzia zeylanica var. microphylla (Wedd.) Masam, Urticaceae, on skin infections in mice. FPZ ointment anti-infective effect was investigated on Staphylococcus aureus-induced skin abscess and skin ulcers in mice by evaluating the variation in abscess volume, histopathology of skin tissue and healing rate. Secondary, it is topical anti-inflammatory activities on carrageenan-induced hind paw edema in mice was estimated. Besides, FPZ ointment fingerprint was performed by using ultra-performance liquid chromatography and FPZ ointment chemical constituents were isolated and identified by repeated column chromatograph and spectroscopic methods. The results revealed that FPZ ointment topical application at the concentration of 2.5-10% could attenuate skin abscess and ulcers and accelerate wound healing, as compared with control group treated with vehicle (p < 0.05). The histological analysis indicated that FPZ ointment acted via inflammation inhibition, granulation promotion and epidermis formation. Moreover, FPZ ointment effectively inhibited carrageenan-induced paw edema in a dose-dependent manner, especially 10% FPZ which showed superior activities in comparison with dexamethasone used as reference drug. FPZ ointment topical application showed a significant anti-infective effect against pyogenic bacterial skin infection in mice.

Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence.

During embryonic brain development, neural progenitor/stem cells (NPCs) sequentially give rise to different subtypes of neurons and glia via a highly orchestrated process. To accomplish the ordered generation of distinct progenies, NPCs go through multistep transitions of their developmental competence. The molecular mechanisms driving precise temporal coordination of these transitions remains enigmatic. Epigenetic regulation, including changes in chromatin structures, DNA methylation, and histone modifications, has been extensively investigated in the context of cortical neurogenesis. Recent studies of chemical modifications on RNA, termed epitranscriptomics, have also revealed their critical roles in neural development. In this review, we discuss advances in understanding molecular regulation of the sequential lineage specification of NPCs in the embryonic mammalian brain with a focus on epigenetic and epitranscriptomic mechanisms. In particular, the discovery of lineage-specific gene transcripts undergoing rapid turnover in NPCs suggests that NPC developmental fate competence is determined much earlier, before the final cell division, and is more tightly controlled than previously appreciated. We discuss how multiple regulatory systems work in harmony to coordinate NPC behavior and summarize recent findings in the context of a model of epigenetic and transcriptional prepatterning to explain NPC developmental competence.

Effects of monosulfuron-ester on metabolic processes of nitrogen-fixing cyanobacteria Anabaena flos-aquae and Anabaena azotica

Presence of the relatively new sulfonylurea herbicide monosulfuron-ester at 0.03-300 nmol/L affected the growth of two non-target nitrogen-fixing cyanobacteria (Anabaena flos-aquae and Anabaena azotica) and substantially inhibited in vitro Acetolactate synthase activity, with IC50 of 3.3 and 101.3 nmol/L for A. flos-aquae and A. azotica, respectively. Presenting in 30-300 nmol/L, it inhibited protein synthesis of the cyanobacteria with less amino acids produced as its concentration increased. Our findings support the view that monosulfuron-ester toxicity in both nitrogen-fixing cyanobacteria is due to its interference with protein metabolism via inhibition of branch-chain amino acid biosynthesis, and particularly Acetolactate synthase activity.(AU)

Effects of monosulfuron-ester on metabolic processes of nitrogen-fixing cyanobacteria Anabaena flos-aquae and Anabaena azotica

Abstract Presence of the relatively new sulfonylurea herbicide monosulfuron-ester at 0.03-300 nmol/L affected the growth of two non-target nitrogen-fixing cyanobacteria (Anabaena flos-aquae and Anabaena azotica) and substantially inhibited in vitro Acetolactate synthase activity, with IC50 of 3.3 and 101.3 nmol/L for A. flos-aquae and A. azotica, respectively. Presenting in 30-300 nmol/L, it inhibited protein synthesis of the cyanobacteria with less amino acids produced as its concentration increased. Our findings support the view that monosulfuron-ester toxicity in both nitrogen-fixing cyanobacteria is due to its interference with protein metabolism via inhibition of branch-chain amino acid biosynthesis, and particularly Acetolactate synthase activity.

Effects of monosulfuron-ester on metabolic processes of nitrogen-fixing cyanobacteria Anabaena flos-aquae and Anabaena azotica.

Presence of the relatively new sulfonylurea herbicide monosulfuron-ester at 0.03-300nmol/L affected the growth of two non-target nitrogen-fixing cyanobacteria (Anabaena flos-aquae and Anabaena azotica) and substantially inhibited in vitro Acetolactate synthase activity, with IC50 of 3.3 and 101.3nmol/L for A. flos-aquae and A. azotica, respectively. Presenting in 30-300nmol/L, it inhibited protein synthesis of the cyanobacteria with less amino acids produced as its concentration increased. Our findings support the view that monosulfuron-ester toxicity in both nitrogen-fixing cyanobacteria is due to its interference with protein metabolism via inhibition of branch-chain amino acid biosynthesis, and particularly Acetolactate synthase activity.

Efficacy and Safety of Rituximab in Systemic Lupus Erythematosus and Sjögren Syndrome Patients With Refractory Thrombocytopenia: A Retrospective Study of 21 Cases.

OBJECTIVE: Recent studies suggested a potential of rituximab (RTX) in treating autoimmune thrombocytopenia (AITP) secondary to autoimmune diseases. In this study, we retrospectively evaluated the efficacy and safety of RTX therapy in patients with refractory AITP secondary to systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). METHODS: Twenty-one SLE and/or SS patients with treatment-resistant AITP were treated once or repeatedly with RTX at the Rheumatology Clinic Renji Hospital, during the period March 2012 to June 2014. Clinical and laboratory variables recorded at every follow-up visit were analyzed. RESULTS: The median age of all patients was 37.05 ± 3.15 years (range, 13-67 years; 20 female and 1 male). The median AITP duration before RTX treatment was 5.46 years. Previous treatments of 21 patients included immunosuppressive agents such as corticosteroids (n = 19), cyclosporine (n = 9), mycophenolate mofetil (n = 2), methotrexate (n = 3), cyclophosphamide (n = 2), vincristine (n = 3), and hydroxychloroquine (n = 15), and 7 patients received concomitantly intravenous immunoglobulin therapy. Two patients had undergone splenectomy without improvement. Seventeen patients (80.95%) were treated repeatedly with RTX during the follow-up period. The overall response rate to RTX treatment (including complete response, 52.38%; partial response, 28.57%) was 80.95%. A significant increase (P < 0.05) of platelet counts was seen after 1 month (median, 32.24 × 10/mL vs 66.53 × 10/mL). Relapses occurred mostly during the first 9 months, and maintaining duration of response was 10.27 months (range, 2-17 months) on average after the first RTX infusion. Antiplatelet antibodies, especially IgG isotype, decreased significantly (P < 0.05) after RTX treatment. No adverse effects were observed among 15 patients (71.4%); however, 2 cases died of severe pneumonia, and another developed lymphoma. CONCLUSIONS: Rituximab is an additional potent therapeutic treatment option for SLE and SS patients with AITP refractory to conventional immunosuppressive treatments. For most patients, RTX was safe and well tolerated.

The diameter of the originating vein determines esophageal and gastric fundic varices in portal hypertension secondary to posthepatitic cirrhosis.

OBJECTIVE: The aim of this study was to determine whether and how the diameter of the vein that gives rise to the inflowing vein of the esophageal and gastric fundic varices secondary to posthepatitic cirrhosis, as measured with multidetector-row computed tomography, could predict the varices and their patterns. METHODS: A total of 106 patients with posthepatitic cirrhosis underwent multidetector-row computed tomography. Patients with and without esophageal and gastric fundic varices were enrolled in Group 1 and Group 2, respectively. Group 1 was composed of Subgroup A, consisting of patients with varices, and Subgroup B consisted of patients with varices in combination with portal vein-inferior vena cava shunts. The diameters of the originating veins of veins entering the varices were reviewed and statistically analyzed. RESULTS: The originating veins were the portal vein in 8% (6/75) of patients, the splenic vein in 65.3% (49/75) of patients, and both the portal and splenic veins in 26.7% (20/75) of patients. The splenic vein diameter in Group 1 was larger than that in Group 2, whereas no differences in portal vein diameters were found between groups. In Group 1, the splenic vein diameter in Subgroup A was larger than that in Subgroup B. A cut-off splenic vein diameter of 8.5 mm achieved a sensitivity of 83.3% and specificity of 58.1% for predicting the varices. For discrimination of the varices in combination with and without portal vein-inferior vena cava shunts, a cut-off diameter of 9.5 mm achieved a sensitivity of 66.7% and specificity of 60.0%. CONCLUSION: The diameter of the splenic vein can be used to predict esophageal and gastric fundic varices and their patterns.

The diameter of the originating vein determines esophageal and gastric fundic varices in portal hypertension secondary to posthepatitic cirrhosis

OBJECTIVE: The aim of this study was to determine whether and how the diameter of the vein that gives rise to the inflowing vein of the esophageal and gastric fundic varices secondary to posthepatitic cirrhosis, as measured with multidetector-row computed tomography, could predict the varices and their patterns. METHODS: A total of 106 patients with posthepatitic cirrhosis underwent multidetector-row computed tomography. Patients with and without esophageal and gastric fundic varices were enrolled in Group 1 and Group 2, respectively. Group 1 was composed of Subgroup A, consisting of patients with varices, and Subgroup B consisted of patients with varices in combination with portal vein-inferior vena cava shunts. The diameters of the originating veins of veins entering the varices were reviewed and statistically analyzed. RESULTS: The originating veins were the portal vein in 8% (6/75) of patients, the splenic vein in 65.3% (49/75) of patients, and both the portal and splenic veins in 26.7% (20/75) of patients. The splenic vein diameter in Group 1 was larger than that in Group 2, whereas no differences in portal vein diameters were found between groups. In Group 1, the splenic vein diameter in Subgroup A was larger than that in Subgroup B. A cut-off splenic vein diameter of 8.5 mm achieved a sensitivity of 83.3% and specificity of 58.1% for predicting the varices. For discrimination of the varices in combination with and without portal vein-inferior vena cava shunts, a cut-off diameter of 9.5 mm achieved a sensitivity of 66.7% and specificity of 60.0%. CONCLUSION: The diameter of the splenic vein can be used to predict esophageal and gastric fundic varices and their patterns.