Curative effect of the total saponins of Panax japonicus (TSPJ) on type 2 diabetes: Focusing on VEGFA.

OBJECTIVE: The objective of this study was to assess the impact of the total saponins of Panax japonicus (TSPJ) on Type 2 diabetes mellitus (T2DM). RESULTS: The intervention of TSPJ was found to have the ability to reverse physiological indicators associated with T2DM, while also enhancing the expression of genes involved in glucose metabolism and intestinal homeostasis. Additionally, alterations in the composition of the gut microbiota were observed. Based on the findings of experimental results and network pharmacology analysis, it is evident that vascular endothelial growth factor A (VEGFA) serves as a prominent shared target between TSPJ and diabetes. The outcomes observed in T2DM mice overexpressing VEGFA align with those observed in T2DM mice treated with TSPJ. CONCLUSIONS: TSPJ administration and VEGFA overexpression yield similar effects on T2DM in mice. Thus, in terms of mechanism, by upregulating the expression of VEGFA, TSPJ may ameliorate metabolic imbalance, preserve intestinal homeostasis, and lessen the symptoms of type 2 diabetes. The findings demonstrated the viability of using VEGFA as a type 2 diabetes therapy option and offered important insights into the therapeutic mechanisms by TSPJ in the management of T2DM. To determine the exact mechanisms behind the effects of TSPJ and VEGFA and to assess their potential therapeutic uses, more research efforts are necessary.

Immune checkpoint inhibitor induced colitis and arthritis: A case report.

RATIONALE: As a programmed cell death 1 (PD-1) inhibitor, camrelizumab is used in the treatment of a variety of malignancies. However, a variety of immune-mediated adverse reactions have been reported in a wide range of clinical applications, including immune-related colitis, arthritis, hepatitis, etc. PATIENT CONCERNS: This 56-year-old male patient experienced diarrhea, bloody stool, and knee pain after receiving camrelizumab for metastatic esophageal squamous cell carcinoma. Colonoscopy showed granular changes in the whole colonic mucosa and blurred or even disappeared vascular texture. Pathology showed chronic inflammation of the colonic mucosa. Magnetic resonance imaging of knee joint showed exudative inflammatory changes in bilateral knee joints. DIAGNOSIS: Immune checkpoint inhibitor-induced colitis and arthritis. INTERVENTIONS: Mesalazine oral (extended-release granules, 1000 mg/quarter in die daily). Dexamethasone sodium phosphate (once daily, 5mg in the evening) and compound cypress liquid (once daily, 100ml in the evening) were given by enema. Anti-inflammatory and analgesic treatment of bone pain plaster. OUTCOMES: The patient had diarrhea reduced to 3 times/day, no more bloody stools, and the knee pain was relieved. LESSONS: This article describes the cases of immune-related colitis and arthritis caused by camrelizumab, and recommends considering the risk of colitis and arthritis with camrelizumab monotherapy or combination therapy.

The impact of human cadaveric dissection on professional identity formation in medical students.

BACKGROUND: As technology advances, some schools are moving away from human cadaveric dissection to teach anatomy, leading to concern regarding the possible loss of a professional identity building experience. This study explored the role of dissection in students' professional identity formation. METHODS: A mixed-methods study was conducted using survey methodology and semi-structured interviews of medical students at an American-style graduate-entry medical school in Singapore. The questionnaire adopted the conceptual framework of the Ring Theory of Personhood and the MacLeod-Clark Professional Identity Scale was used to measure professional identity, followed by semi-structured interviews of students using Braun and Clarke's six-phase reflexive thematic analysis. RESULTS: Respondents did not differ substantively from non-respondents by age, nationality, or ethnicity, and year of entering medical school, however, they were slightly more female dominant. The number of hours of hands-on participation in dissection showed no significant relationship (r2 = 0.010; p = 0.424) with professional identity formation measured by the MacLeod-Clark Professional Identity Scale. Despite the survey results, semi-structured interviews revealed rich and nuanced findings suggesting the influence of dissection in participants' professional identity formation through deepening students' appreciation of humanistic values and enhancing their notions of patients' personhood. Notably, students without dissection experience did not express these sentiments and were orientated towards knowledge acquisition. CONCLUSION: While our findings do not suggest that dissection strongly impacts students' professional identity formation, students shared thought-provoking experiences which suggest some level of its contribution. Careful consideration of this phenomenon should be exercised prior to removing dissection in favour of technological alternatives.

Antiepileptic drug-induced hypersensitivity syndrome with liver function abnormality and fever as the first manifestation: A case report.

RATIONALE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous drug reaction characterized by fever, lymphadenopathy, hematologic abnormalities, single or multiple organ involvement, and viral reactivation.[1] The most frequently reported offending drugs are aromatic antiepileptic agents, antibiotics, and allopurinol.[2] Though a relatively rare syndrome, DRESS can lead to severe multi-organ system dysfunction, and in some cases even death. DRESS is one of the severe drug eruptions in dermatological diseases, but it is difficult to diagnose for internist. In this paper, a typical drug hypersensitivity syndrome with abnormal liver function and fever as the first manifestations was reported. The objective of this study was to improve the understanding of rare drug hypersensitivity syndrome in digestion and other fields, and to avoid missed diagnosis and misdiagnosis. PATIENT CONCERNS: A 33-year-old Chinese female was initially diagnosed with acute hepatic insufficiency. Combined with the suspicious drug history, she developed DRESS with fever, target erythema, left lymph node enlargement, hematological abnormalities, and abnormal liver function. DIAGNOSES: Combined with the above characteristics, liver toxicity is the main manifestation, accompanied by fever, mainly moderate to high fever (above 38 °C) , sporadic rash, other organs (kidney, immune system) damage, and a marked increase in eosinophil granulocytic. Therefore the patient was diagnosed with definite case of DRESS syndrome based on clinical and laboratory findings. INTERVENTIONS: Hormones (methylprednisolone 60 mg/day for 12 days and 80 mg/day for 12 days) and immunoglobulins (intravenous immunoglobulin 10 g/day for 5 days and 20 g/day for 7 days) were given. OUTCOMES: The patient was discharged from the hospital after recovery. One month after discharge, she was re-admitted to the hospital because of elevated blood sugar and was diagnosed as diabetes. LESSONS: DRESS syndrome is a rare but life-threatening hypersensitivity reaction. The mortality will be very high if it's not diagnosed and treated timely. This paper presents a successful case of methylprednisolone plus intravenous immunoglobulin therapy, which provides a stronger evidence for the future diagnosis and treatment of the disease.

Tofacitinib combined with leflunomide for treatment of psoriatic arthritis with IgA nephropathy: a case report with literature review.

Psoriasis is a systemic inflammatory disease that is associated with increased risk of several diseases, such as psoriatic arthritis (PsA), inflammatory bowel disease, and cardiovascular diseases. About 20 to 30% patients with psoriasis subsequently develop PsA. IgA nephropathy is the most common primary glomerular disease world-wide. Psoriasis and IgA nephropathy appear to be associated, but the mechanism underlying this connection is unclear. Tofacitinib and leflunomide are common treatments for psoriatic arthritis. We administered tofacitinib combined with leflunomide to a 38-year-old female patient who presented with PsA and IgA nephropathy. After treatment, she experienced significant reductions in the psoriatic lesions, pain in the right knee joint, and proteinuria. Administration of tofacitinib combined with leflunomide for treatment of a patient who had PsA complicated with IgA nephropathy led to significant resolution of the symptoms of both conditions. These results suggest similarities in the pathogenesis of PsA and IgA nephropathy and a possible new treatment for IgA nephropathy.

The role of Elabela in kidney disease.

Elabela, also known as Toddler or Apela, is a recently discovered hormonal peptide containing 32 amino acids. Elabela is a ligand of the apelin receptor (APJ). APJ is a G protein-coupled receptor widely expressed throughout body, and together with its cognate ligand, apelin, it plays an important role in various physiological processes including cardiovascular functions, angiogenesis and fluid homeostasis. Elabela also participates in embryonic development and pathophysiological processes in adulthood. Elabela is highly expressed in undifferentiated embryonic stem cells and regulates endoderm differentiation and cardiovascular system development. During differentiation, Elabela is highly expressed in pluripotent stem cells and in adult renal collecting ducts and loops, where it functions to maintain water and sodium homeostasis. Other studies have also shown that Elabela plays a crucial role in the pathogenesis of kidney diseases. This review addresses the role of Elabela in kidney diseases including renal ischemia/reperfusion injury, hypertensive nephropathy, diabetic nephropathy, and cardiorenal syndrome.

Differential expression analysis of urinary exosomal circular RNAs in patients with IgA nephropathy.

AIMS: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease to cause end-stage kidney disease. This study investigated the difference in urinary exosomal circular RNA (circRNA) expression profiles between patients with IgAN and healthy controls (HCs), for better understanding of gene regulation in exosomes of IgAN patients. METHODS: A pairwise comparison of urinary circRNA expression profiles between IgAN patients and HCs was performed using methods, including high-throughput sequencing and quantitative polymerase chain reaction. Moreover, the potential functions of differentially expressed circRNAs (DECs) in IgAN were investigated by gene ontology (GO) enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; and the circRNA-miRNA-mRNA network. RESULTS: We identified 450 upregulated and 26 downregulated circRNAs in the IgAN patients. GO analysis showed that these enriched circRNAs might regulate primary miRNA processing, the ability of angiotensin receptor binding, and stress fibre function. KEGG analysis suggested these DECs may be closely associated with the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-Akt) signalling pathways. Network analysis revealed the relationship between circRNAs and their target genes. CONCLUSION: The identified DECs may be useful for both researches on molecular aetiology of IgAN and development of potentially novel non-invasive biomarkers of IgAN.

Effects of Zuogui Pills and Yougui Pills on Caspase-3/Bcl-2 of BMSCs in ovariectomized rats after osteogenic and adipogenic differentiation / 中成药

AIM To observe the effects of Zuogui Pills and Yougui Pills on the proliferation of BMSCs and the expression of apoptosis after osteogenic and adipogenic differentiation in ovariectomized rats.METHODS Of sixty female SD rats,forty rats followed by bilateral ovariectomy were randomly divided into ovariectomy group (1.0 g/kg distilled water),Zuogui Pills group (9.45 g/kg Zuogui Pills) and Yougui Pills group (10.26 g/kg Yougui Pills) and Bujiale group (0.09 mg/kg estradiol valerate),another ten rats as control group (1.0 g/kg distilled water),ten rats bilateral excision of a small amount of fat around the ovary was treated as sham operation group (1.0 g/kg distilled water).After 12 weeks of administration,the rats were killed,BMSCs were cultured in vitro.Cell proliferation was detected by MTT assay.Western blot was used to detect the protein expressions of Caspase-3 and Bcl-2.RE-SULTS MTT assay showed that the proliferation of BMSCs were promoted in Zuogui and Yougui Pills groups,and the proliferation effect in Zuogui Pills group was better than that in Yougui Pills group.After osteogenic differentiation,as compared with the control group,the Caspase-3 expression of ovariectomy group was up-regulated (P ＜0.05) and the expression of Bcl-2 was down-regulated (P ＜0.01).As compared with ovariectomy group,the expression of Caspase-3 was decreased and the expression of Bcl-2 was up-regulated in Zuogui Pills group and Yougui Pills group.After adipogenic differentiation,as compared with the control group,the expressions of Caspase-3 were significantly up-regulated and Bcl-2 were down-regulated in the ovariectomy group,Zuogui Pills group and Yougui Pills group (P ＜ 0.05).After osteogenic and adipogenic differentiation Zuogui Pills group and Yougui Pills group were significant different (P ＜ 0.05).CONCLUSION Zuogui Pills and Yougui Pills both can inhibit the apoptosis of BMSCs after osteogenic and adipogenic differentiation in ovariectomized rats.Zuogui Pills can promote BMSCs osteogenesis differentiation while Yougui Pills can promote adipogenic differentiation.

Effects of Zuogui Pills and Yougui Pills on Caspase-3/Bcl-2 of BMSCs in ovariectomized rats after osteogenic and adipogenic differentiation / 中成药

AIM To observe the effects of Zuogui Pills and Yougui Pills on the proliferation of BMSCs and the expression of apoptosis after osteogenic and adipogenic differentiation in ovariectomized rats.METHODS Of sixty female SD rats,forty rats followed by bilateral ovariectomy were randomly divided into ovariectomy group (1.0 g/kg distilled water),Zuogui Pills group (9.45 g/kg Zuogui Pills) and Yougui Pills group (10.26 g/kg Yougui Pills) and Bujiale group (0.09 mg/kg estradiol valerate),another ten rats as control group (1.0 g/kg distilled water),ten rats bilateral excision of a small amount of fat around the ovary was treated as sham operation group (1.0 g/kg distilled water).After 12 weeks of administration,the rats were killed,BMSCs were cultured in vitro.Cell proliferation was detected by MTT assay.Western blot was used to detect the protein expressions of Caspase-3 and Bcl-2.RE-SULTS MTT assay showed that the proliferation of BMSCs were promoted in Zuogui and Yougui Pills groups,and the proliferation effect in Zuogui Pills group was better than that in Yougui Pills group.After osteogenic differentiation,as compared with the control group,the Caspase-3 expression of ovariectomy group was up-regulated (P ＜0.05) and the expression of Bcl-2 was down-regulated (P ＜0.01).As compared with ovariectomy group,the expression of Caspase-3 was decreased and the expression of Bcl-2 was up-regulated in Zuogui Pills group and Yougui Pills group.After adipogenic differentiation,as compared with the control group,the expressions of Caspase-3 were significantly up-regulated and Bcl-2 were down-regulated in the ovariectomy group,Zuogui Pills group and Yougui Pills group (P ＜ 0.05).After osteogenic and adipogenic differentiation Zuogui Pills group and Yougui Pills group were significant different (P ＜ 0.05).CONCLUSION Zuogui Pills and Yougui Pills both can inhibit the apoptosis of BMSCs after osteogenic and adipogenic differentiation in ovariectomized rats.Zuogui Pills can promote BMSCs osteogenesis differentiation while Yougui Pills can promote adipogenic differentiation.

Protective effect of esculentoside A on lipopolysaccharide-induced acute lung injury in mice.

BACKGROUND: Esculentoside A (EsA) is a saponin isolated from the Chinese herb Phytolacca esculenta. In our study, we sought to investigate the protective effects of EsA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. MATERIALS AND METHODS: To determine the effects of EsA on the reduction of histopathologic changes in mice with ALI, inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet-to-dry weight ratio were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. Next, cytokine production induced by LPS in BALF was measured by enzyme-linked immunosorbent assay. To further study the mechanism of EsA protective effects on ALI, IκBa, p38, and extracellular signal receptor-activated kinase pathways were investigated in lung tissue of mice with ALI. RESULTS: In the present investigation, EsA showed marked effects by reducing inflammatory infiltration, thickening of the alveolar wall, and pulmonary congestion. Levels of tumor necrosis factor α and interleukin 6 elevated by LPS were significantly decreased in BALF in EsA-pretreated ALI model. Furthermore, EsA significantly suppressed phosphorylation of IκBa, p38, and extracellular signal receptor-activated kinase. CONCLUSIONS: Taken together, our results suggest that EsA suppressed inflammatory responses in LPS-induced ALI through inhibition of the nuclear factor kappa B and mitogen activated protein kinase signaling pathways. EsA may be a promising potential preventive agent for ALI treatment.

Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice.

Phillyrin (Phil) is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. We tested the hypothesis that Phil modulates pulmonary inflammation in an ALI model induced by LPS. Male BALB/c mice were pretreated with or without Phil before respiratory administration with LPS, and pretreated with dexamethasone as a control. Cytokine release (TNF-α, IL-1ß, and IL-6) and amounts of inflammatory cell in bronchoalveolar lavage fluid (BALF) were detected by ELISA and cell counting separately. Pathologic changes, including neutrophil infiltration, interstitial edema, hemorrhage, hyaline membrane formation, necrosis, and congestion during acute lung injury in mice were evaluated via pathological section with HE staining. To further investigate the mechanism of Phil anti-inflammatory effects, activation of MAPK and NF-κB pathways was tested by western blot assay. Phil pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by Phil pretreatment. In addition, Phil decreased the production of the proinflammatory cytokines including (TNF-α, IL-1ß, and IL-6) and the concentration of myeloperoxidase (MPO) in lung tissues. Phil pretreatment also significantly suppressed LPS-induced activation of MAPK and NF-κB pathways in lung tissues. Taken together, the results suggest that Phil may have a protective effect on LPS-induced ALI, and it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways. Phil may be a new preventive agent of ALI in the clinical setting.

Isolation of two new prenylflavonols from Epimedium brevicornum and their effects on cytokine production in vitro.

In an attempt to search for bioactive natural products, two new prenylflavonols, 2''-hydroxy-3''-en-anhydroicaritin (1) and 2''-hydroxy-beta-anhydroicaritin (2), were isolated from the Chinese medicinal herb Epimedium brevicornum. Their structures were determined by 1D and 2D NMR spectroscopic analysis. The effects of compounds 1 and 2 on cytokine production in vitro were investigated. Compound 1 could significantly downregulate tumor necrosis factor-alpha (TNF-alpha) production and increase interleukin-10 (IL-10) production. These results suggested that compound 1 may have anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated mouse macrophages. In addition, the biogenetic relationships among compounds 1 and 2 are discussed.

Analysis of digenic epistatic effects and QE interaction effects QTL controlling grain weight in rice.

Immortalized F(2) population of rice (Oryza sativa L.) was developed by randomly mating F(1) among recombinant inbred (RI) lines derived from (Zhenshan 97B x Minghui 63), which allowed replications within and across environments. QTL (quantitative trait loci) mapping analysis on kilo-grain weight of immortalized F(2) population was performed by using newly developed software for QTL mapping, QTLMapper 2.0. Eleven distinctly digenic epistatic loci included a total of 15 QTL were located on eight chromosomes. QTL main effects of additive, dominance, and additive x additive, additive x dominance, and dominance x dominance interactions were estimated. Interaction effects between QTL main effects and environments (QE) were predicted. Less than 40% of single effects, most of which were additive effects, for identified QTL were significant at 5% level. The directional difference for QTL main effects suggested that these QTL were distributed in parents in the repulsion phase. This should make it feasible to improve kilo-grain weight of both parents by selecting appropriate new recombinants. Only few of the QE interaction effects were significant. Application prospect for QTL mapping achievements in genetic breeding was discussed.