The potential impact of 6PPD and its oxidation product 6PPD-quinone on human health: A case study on their interaction with human serum albumin.

6PPD and its oxidation product, 6PPD-quinone have garnered widespread attention due to their adverse effects on aquatic ecosystems and human health, and are recognized as emerging pollutants. In this study, we investigated the interaction mechanism between 6PPD/6PPD-quinone and human serum albumin (HSA) through various experiments. Experimental findings reveal that the IC50 values of 6PPD-quinone and 6PPD against HEK293T cells were 11.78 and 40.04 µM, respectively. Additionally, the cytotoxicity of these compounds was regulated by HSA, displaying an inverse correlation with their binding affinity to HSA. Furthermore, 6PPD/6PPD-quinone can spontaneously insert into site I on HSA, forming a binary complex that induces changes in the secondary structure of HSA. However, their effects on the esterase-like activity of HSA exhibit a dichotomy. While 6PPD activates the esterase-like activity of HSA, 6PPD-quinone inhibits it. Molecular docking analyses reveal that both 6PPD and 6PPD-quinone interact with many amino acid residues on HSA, including TRP214, ARG222, ARG218, ALA291, PHE211. The π electrons on the benzene rings of 6PPD/6PPD-quinone play pivotal roles in maintaining the stability of complexes. Moreover, the stronger binding affinity observed between 6PPD and HSA compared to 6PPD-quinone, may be attributed to the larger negative surface potential of 6PPD.

The dual role of SUSD2 in cancer development.

Sushi domain-containing protein 2 (SUSD2, also known as the complement control protein domain) is a representative and vital protein in the SUSD protein family involved in many physiological and pathological processes beyond complement regulation. Cancer is one of the leading causes of death worldwide. The complex role of SUSD2 in tumorigenesis and cancer progression has raised increasing concerns. Studies suggest that SUSD2 has different regulatory tendencies among different tumors and exerts its biological effects in a cancer type-specific manner; for instance, it has oncogenic effects on breast cancer, gastric cancer, and glioma and has tumor-suppression effects on lung cancer, bladder cancer, and colon cancer. Moreover, SUSD2 can be regulated by noncoding RNAs, its promoter methylation and other molecules, such as Galectin-1 (Gal-1), tropomyosin alpha-4 chain (TPM4), and p63. The therapeutic implications of targeting SUSD2 have already been preliminarily revealed in some malignancies, including melanoma, colon cancer, and breast cancer. This article reviews the role and regulatory mechanisms of SUSD2 in cancer development, as well as its structure and distribution. We hope that this review will advance the understanding of SUSD2 as a diagnostic and/or prognostic biomarker and provide new avenues for the development of novel cancer therapies.

Effects of Extracellular Vesicles Derived from Human Umbilical Cord Blood Mesenchymal Stem Cells on Cell Immunity in Nonobese Mice.

Autoimmune responses are the most important pathogenic mechanisms underlying type 1 diabetes (T1D). Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have immunomodulatory effects. In this study, we investigated whether EVs derived from human umbilical cord MSCs (HucMSC-EVs) have treatment effects on nonobese diabetic (NOD) mice as model of T1D. HucMSC-EVs were isolated from human umbilical cord MSCs and characterized. NOD mice (aged 4 weeks) were administered with HucMSC-EVs or the same volume of phosphate-buffered saline (PBS) via caudal vein injection twice per week. After 8 weeks of treatment, blood, spleen, and pancreatic samples were collected. Mouse blood glucose levels and body weights were measured during treatment, and insulin concentration and inflammatory cytokine levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) staining were used to evaluate pathological changes in mouse islets. T lymphocyte subsets were evaluated by flow cytometry, while quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analyses were used to detect the expression of transcription factor and inflammatory cytokines. Our data indicated that HucMSC-EVs treatment reduced blood glucose levels and increased insulin concentration in NOD mice. Levels of interleukin-2 (IL-2), IL-4, and IL-10 were significantly increased and those of IL-1ß and interferon-γ (IFN-γ) significantly decreased in the HucMSC-EVs group. The positive ratio of CD4+ T lymphocyte subsets decreased after intravenous injection of HucMSC-EVs, in which the proportion of Th2 cells increased and that of Th1 decreased. GATA-3 and IL-2, IL-4 and IL-10 expression levels were upregulated in spleen on treatment with HucMSC-EVs, whereas those of T-bet and IFN-γ were downregulated. In addition, more inflammatory cell infiltration was detected in the pancreas of control group mice than those treated with HucMSC-EVs. IHC staining showed that Fas/FasL expression and distribution in control group pancreas were higher than those in the HucMSC-EVs group. Together, our findings indicate that HucMSC-EVs have potential to prevent islet injury via T cell immune responses by adjusting the Th1/Th2 ratio to regulate secretion of inflammatory factors.

Case report: Noonan syndrome with protein-losing enteropathy.

Background: Noonan syndrome (NS) is characterized by typical facial features, short stature, congenital heart defects and other comorbidities. Lymphedema and chylous pleural effusions are also common in NS, but protein-losing enteropathy (PLE) is rarely reported. Case presentation: We present the case of a 19-year-old Chinese woman presenting with PLE. Small intestine biopsy showed obvious expansion of lymphatic vessels. The gene mutation results of the patient indicated a c.184T>G missense mutation (p.Tyr62Asp) in the PTPN11 gene (NM_002834.3). Conclusion: NS accompanied by PLE is not common, but hypoproteinemia attributable to PLE may be more common in patients with NS than previously thought. It remains uncertain whether mutation of the PTPN11 gene is related to PLE, indicating that further research is needed.

Interferon-gamma treatment of human umbilical cord mesenchymal stem cells can significantly reduce damage associated with diabetic peripheral neuropathy in mice.

BACKGROUND: Diabetic peripheral neuropathy causes significant pain to patients. Umbilical cord mesenchymal stem cells have been shown to be useful in the treatment of diabetes and its complications. The aim of this study was to investigate whether human umbilical cord mesenchymal stem cells treated with interferon-gamma can ameliorate nerve injury associated with diabetes better than human umbilical cord mesenchymal stem cells without interferon-gamma treatment. METHODS: Human umbilical cord mesenchymal stem cells were assessed for adipogenic differentiation, osteogenic differentiation, and proliferation ability. Vonfry and a hot disc pain tester were used to evaluate tactile sensation and thermal pain sensation in mice. Hematoxylin-eosin and TUNEL staining were performed to visualize sciatic nerve fiber lesions and Schwann cell apoptosis in diabetic mice. Western blotting was used to detect expression of the apoptosis-related proteins Bax, B-cell lymphoma-2, and caspase-3 in mouse sciatic nerve fibers and Schwann cells. Real-Time Quantitative PCR was used to detect mRNA levels of the C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10 in mouse sciatic nerve fibers and Schwann cells. Enzyme-linked immunosorbent assay was used to detect levels of the inflammatory cytokines, interleukin-1ß, interleukin-6, and tumor necrosis factor-α in serum and Schwann cells. RESULTS: The adipogenic differentiation capacity, osteogenic differentiation capacity, and proliferation ability of human umbilical cord mesenchymal stem cells were enhanced after interferon-gamma treatment. Real-Time Quantitative PCR revealed that interferon-gamma promoted expression of the adipogenic markers, PPAR-γ and CEBP-α, as well as of the osteogenic markers secreted phosphoprotein 1, bone gamma-carboxyglutamate protein, collagen type I alpha1 chain, and Runt-related transcription factor 2. The results of hematoxylin-eosin and TUNEL staining showed that pathological nerve fiber damage and Schwann cell apoptosis were reduced after the injection of interferon-gamma-treated human umbilical cord mesenchymal stem cells. Expression of the apoptosis-related proteins, caspase-3 and Bax, was significantly reduced, while expression of the anti-apoptotic protein B-cell lymphoma-2 was significantly increased. mRNA levels of the cell chemokines, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10, were significantly reduced, and levels of the inflammatory cytokines, interleukin-1ß, interleukin-6, and tumor necrosis factor-α, were decreased. Tactile and thermal pain sensations were improved in diabetic mice. CONCLUSION: Interferon-gamma treatment of umbilical cord mesenchymal stem cells enhanced osteogenic differentiation, adipogenic differentiation, and proliferative potential. It can enhance the ability of human umbilical cord mesenchymal stem cells to alleviate damage to diabetic nerve fibers and Schwann cells, in addition to improving the neurological function of diabetic mice.

Female is Associated with Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes.

Aim: Diabetic cardiomyopathy is a subset of heart disease that is directly associated with diabetes, and left ventricular diastolic dysfunction is the earliest sign. We aimed to investigate the association between sex differences and left ventricular diastolic function in patients with type 2 diabetes. Methods: This was a cross-sectional study included patients with type 2 diabetes who visit the National Metabolic Management Center (MMC) at the First People's Hospital of Yunnan from 2018 to 2021. Patients with hypertension, history of heart disease or ejection fraction <50% were excluded from the study. Logistic regression was used to analyze their associations. Results: A total of 1778 patients were included in the study. The study included 1205 (70%) males and 573 (30%) females. Compared with males, females had higher total cholesterol and LDL cholesterol levels but lower diastolic pressure, body mass index (BMI), visceral fat area, HbA1c, blood urea nitrogen (BUN), serum creatinine and triglyceride. Females had a relatively higher ejection fraction than males (68.17 ± 6.055 vs 67.5 ± 6.096, P < 0.05). More female patients than male patients in the age group of 45-60 years old had left ventricular diastolic dysfunction (female vs male, 54.5% vs 46.9%, P < 0.05). We also found that females were independently associated with left ventricular diastolic dysfunction, after adjusting for important clinical factors. Conclusion: Left ventricular diastolic function might be worse in female patients with type 2 diabetes. Further study is needed to verify the underlying mechanism.

Annexin A3 accelerates osteoclast differentiation by promoting the level of RANK and TRAF6.

Annexin A3 (ANXA3), a member of Annexin family, is reported to mediate membrane transport and cancer development. However, the effect of ANXA3 on osteoclast formation and bone metabolism is still unclear. In this study, we found that knockdown of ANXA3 can significantly inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation through NF-κB signaling. ANXA3 downregulation abrogated the expression of osteoclast-specific genes, including Acp5, Mmp9 and Ctsk in osteoclast precursors. Moreover, lentiviral of shRNA against ANXA3 reversed the bone loss in osteoporosis using ovariectomized mice model. Mechanistically, we found that ANXA3 directly bound to RANK and TRAF6 to accelerate osteoclast differentiation by promoting their transcription and limiting degradation. In conclusion, we propose a fundamentally novel RANK-ANXA3-TRAF6 complex to effectively modulate the formation and differentiation of osteoclast to manipulate bone metabolism. The ANXA3-targeted therapeutic strategy may provide new insight for bone degrading-related diseases prevention and treatment.

Case report: A heterozygous mutation in ZNF462 leads to growth hormone deficiency.

Weiss-Kruszka syndrome (WSKA) is a rare disease most often caused by mutations in the ZNF462 gene. To screen for hereditary diseases, exons from the patient's genome were sequenced. Genomic PCR experiments followed by Sanger sequencing were used to confirm the mutated genomic regions in the patient and his parents. We report a new mutation site, a heterozygous mutation (NM_021224.6:c.6311dup) in ZNF462 in a male patient of 8 years old. The mutation in the ZNF462 gene caused WSKA. This patient is the first case with WSKA characterized by attention-deficit hyperactivity disorder and complete growth hormone deficiency without pituitary lesions. Our results suggest that the heterozygous mutation in ZNF462 is the direct cause of WSKA in this patient. Mutations in other genes interacting with ZNF462 result in similar symptoms of WSKA. Furthermore, ZNF462 and its interacting proteins ASXL2 and VPS13B may form a protein complex that is important for normal development but awaits more studies to reveal its detailed functions.

FGF2 isoforms play distinct roles in tubular epithelial-to-mesenchymal transition in diabetic nephropathy.

INTRODUCTION: The role of different isoforms of Fibroblast growth factor-2 (FGF2) in tubular epithelial-to-mesenchymal transition (EMT) in diabetic nephropathy remains unknown. We aimed to evaluate the role of FGF2 isoforms in the pathogenesis of EMT. MATERIALS AND METHODS: Western blot and immunofluorescence were used to assess the expression of FGF2 isoforms in db/db mice and high glucose-stimulated HK2 cells. The effects of specific FGF2 isoforms on EMT were explored via overexpression or knockdown of the corresponding isoform in HK2 cells cultivated in high glucose. RESULTS: Expression of low molecular weight (LMW) FGF2 was up-regulated while high molecular weight (HMW) FGF2 was down-regulated in the kidney of db/db mice and HK2 cells cultured in high glucose that underwent EMT. Overexpression of the LMW FGF2 enhanced EMT changes, while overexpression of the HMW FGF2 attenuated EMT. Knockdown of HMW FGF2 in HK2 cells promoted the EMT process. CONCLUSIONS: The expression and function of LMW and HMW FGF2 differed in the process of EMT in tubular cells. LMW FGF2 contributed to EMT, while HMW FGF2 played a protective role in the EMT process.

Mechanical force-promoted osteoclastic differentiation via periodontal ligament stem cell exosomal protein ANXA3.

Exosomes play a critical role in intracellular communication. The biogenesis and function of exosomes are regulated by multiple biochemical factors. In the present study, we find that mechanical force promotes the biogenesis of exosomes derived from periodontal ligament stem cells (PDLSCs) and alters the exosomal proteome profile to induce osteoclastic differentiation. Mechanistically, mechanical force increases the level of exosomal proteins, especially annexin A3 (ANXA3), which facilitates exosome internalization to activate extracellular signal-regulated kinase (ERK), thus inducing osteoclast differentiation. Moreover, the infusion of exosomes derived from PDLSCs into mice promotes mechanical force-induced tooth movement and increases osteoclasts in the periodontal ligament. Collectively, this study demonstrates that mechanical force treatment promotes the biogenesis of exosomes from PDLSCs and increases exosomal protein ANXA3 to facilitate exosome internalization, which activates ERK phosphorylation, thus inducing osteoclast differentiation. Our findings shed light on new mechanisms for how mechanical force regulates the biology of exosomes and bone metabolism.

A New Way Out of the Predicament of Anaplastic Thyroid Carcinoma From Existing Data Analysis.

Background: Anaplastic thyroid carcinoma (ATC) is an endocrine tumor with a low incidence but a very poor prognosis. The vast majority of patients have a survival time of only three to six months, but a few survive for two years or more. In recent years, there have been major breakthroughs in targeted and immunotherapy in the field of oncology therapy. Although the preliminary study for ATC showed a promising prospect, more clinical trials are needed. It is the best approach to explore the measures that can improve survival time of ATC from the available clinical data, especially those with long survival. Methods: We report on an 82-year-old ATC patient who survived for 3 years and systematically review the clinical characteristics of 45 ATC patients with complete data from the two largest centers in northwest China. In particular, factors related to long-term survival were analyzed and summarized. Results: Three years prior, an 82-year-old woman was diagnosed with ATC by core needle biopsy following a physical examination. The thyroid tumor was resected within one month, and then the patient was treated with radiotherapy. The patient was still healthy after three years of follow-up. Analysis of prognostic factors for the 45 reviewed patients showed that those undergoing radical surgery (median overall survival (OS) = 472 days, p = 0.0261) and radiotherapy (median OS = 220 days, p = 0.0136) had better outcomes. In addition, patients younger than 65 years (median OS = 164.5 days, p = 0.0176) and with a lower tumor stage (IV A, median OS = 633.5 days, p = 0.0191) also had a better outcome. Conclusion: ATC is a highly malignant tumor, but timely early diagnosis and standardized treatment with radical surgery and radiotherapy as the core can achieve good results. Some patients can achieve long-term survival.

Stem Cells From Human Exfoliated Deciduous Teeth Alleviate Liver Cirrhosis via Inhibition of Gasdermin D-Executed Hepatocyte Pyroptosis.

Liver cirrhosis represents a type of end-stage liver disease with few effective therapies, which was characterized by damaged functional liver tissue due to long-term inflammation. Gasdermin D (GSDMD)-executed programmed necrosis is reported to be involved in inflammation. However, the role of GSDMD in liver cirrhosis remains unclear. In this study, we used a CCl4-induced cirrhosis model and found stem cells from human exfoliated deciduous teeth (SHED) infusion showed profound therapeutic effects for liver cirrhosis. Mechanistically, NLRP3 inflammasome-activated GSDMD and its pyroptosis were upregulated in liver cirrhosis, while SHED infusion could suppress the expression of GSDMD and Caspase-1, resulting in reduced hepatocyte pyroptosis and inflammatory cytokine IL-1ß release. Consistently, SHED could inhibit the elevated expression of NLRP3, GSDMD and Caspase-1 induced by CCl4 treatment in vitro co-culture system, which was mediated by decreasing reactive oxygen species (ROS) generation. Moreover, the pyroptosis inhibitor disulfiram showed similar therapeutic effects for liver cirrhosis as SHED. In conclusion, SHED alleviates CCl4-induced liver cirrhosis via inhibition of hepatocytes pyroptosis. Our findings could provide a potential treatment strategy and novel target for liver cirrhosis.

TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer.

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among the triggering receptors expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease-free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not in macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

Association Between Pathophysiological Mechanisms of Diabetic Retinopathy and Parkinson's Disease.

Diabetic retinopathy, the most common complication of diabetes, is a neurodegenerative disease in the eye. And Parkinson's disease, affecting the health of 1-2% of people over 60 years old throughout the world, is the second largest neurodegenerative disease in the brain. As the understanding of diabetic retinopathy and Parkinson's disease deepens, the two diseases are found to show correlation in incidence, similarity in clinical presentation, and close association in pathophysiological mechanisms. To reveal the association between pathophysiological mechanisms of the two disease, in this review, the shared pathophysiological factors of diabetic retinopathy and Parkinson's disease are summarized and classified into dopaminergic system, circadian rhythm, neurotrophic factors, α-synuclein, and Wnt signaling pathways. Furthermore, similar and different mechanisms so far as the shared pathophysiological factors of the two disorders are discussed systematically. Finally, a brief summary and new perspectives are presented to provide new directions for further efforts on the association, exploration, and clinical prevention and treatment of diabetic retinopathy and Parkinson's disease.

Association of Diabetic Peripheral Neuropathy with Vitamin D Levels Depends on Vitamin D Status.

BACKGROUND Vitamin D deficiency has been reported to be associated with diabetic peripheral neuropathy (DPN). Our objective here was to evaluate the association between vitamin D levels and neuropathic symptoms in a Chinese population. MATERIAL AND METHODS A total of 4435 patients with type 2 diabetes (T2D) were recruited in this cross-sectional study. 25-dihydroxyvitamin D (25-(OH) D) serum concentration was measured by electrochemiluminescence assay (Cobas e601, Roche). DPN was clinically diagnosed by assessing neurological symptoms and performing current perception threshold (CPT) testing. Of all the patients, 2910 were CPT-positive and had assessed neurological symptoms. RESULTS In the vitamin D insufficiency group (<30 ng/mL 25-(OH) D), patients with neurological symptoms had higher serum 25-(OH) D levels than those without neurological symptoms (24.65±3.42 ng/mL vs 23.61±4.54 ng/mL, p≤0.001). The risk of numbness and pain increased by 0.5-fold for every 6 ng/mL increase in 25-(OH) D. In the vitamin D sufficiency group (≥30 ng/mL 25-(OH) D), patients with neurological symptoms had lower serum 25-(OH) D levels than those without neurological symptoms (32.96±3.18 ng/mL vs 33.45±4.27 ng/mL, p<0.01). For every 4 ng/mL decrease in 25-(OH) D, the risk of numbness and pain increased by 0.2-fold. CONCLUSIONS The association of neuropathy symptoms with 25-(OH) D levels differed depending on whether the patients had insufficient or sufficient vitamin D.

IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b.

Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified by transmission electron microscope (TEM) and immunofluorescence staining. Administration of exosomes to mice significantly improved the disease activity index and histological score of colitis, and decreased the ratio of Th17 cells with elevated Treg cells ratio in mice colitis model. Exosomes from IFN-γ-primed MSCs showed superior therapeutic effects to colitis. Exosomes treatment inhibited Th17 differentiation in vitro, and exosomes from IFN-γ-primed MSCs showed higher inhibition efficacy. Mechanistically, exosomes treatment significantly decreased the expression of Stat3 and p-Stat3 to inhibit Th17 cells differentiation. IFN-γ pretreatment increased the level of miR-125a and miR-125b of exosomes, which directly targeted on Stat3, to repress Th17 cell differentiation. Moreover, combination of miR-125a and miR-125b agmior infusion also showed therapeutic effects for colitis, accompanied by decreased Th17 cell ratio. Collectively, this study demonstrates that IFN-γ treatment promoted exosomes from MSCs to attenuate colitis through increasing the level of miR-125a and miR-125b, which binding on 3'-UTR of Stat3 to repress Th17 cell differentiation. This study provides a new approach of exocytosis on the treatment of colitis.

[Research Progress of Catheter-based Irreversible Electroporation for Tissue Ablation].

Irreversible electroporation (IRE) is an emerging tissue ablation technique. Compared with thermal ablation technique such as radiofrequency, IRE can achieve focal ablation in a shorter time without heat sink effect while sparing the tissue scaffold. IRE has been demonstrated to be a feasible therapeutic modality for the liver, pancreatic, and prostatic cancer. In recent years, several studies regarding of catheter-directed IRE for digestive tract, bronchus, urinary tract, and myocardium have been performed, which preliminarily demonstrated the safety and efficacy of IRE for tissue ablation under endoscopic or interventional technique. This study summarized the research progress of catheter-directed IRE for tissue ablation. The critical technique and future direction of catheter-based IRE are prosp.

Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis.

BACKGROUND: Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities. AIM: To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms. METHODS: We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms. RESULTS: SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+, CD4+, tumor necrosis-alpha+, and interferon-gamma+ inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis. CONCLUSION: SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.

Unilateral macular choroidal neovascularization-a rare manifestation in acute myelocytic leukemia: Case report.

RATIONALE: Characteristic signs of leukemic retinopathy include bilateral intra-retinal hemorrhage, white-centred hemorrhage, macular hemorrhage and cotton-wool spots. Capillary closure, retinal microaneurysms and neovascularization following massive fundus hemorrhage could be involved in few of the above instances. However, single choroidal neovascularization (CNV) in macular has not been observed in acute myelocytic leukemia (AML). PATIENT CONCERNS: A 22-year-old woman presented with a 7-day history of vision decline in the right eye (OD). The patient was diagnosed as M3 AML one month earlier. Chemotherapy was immediately administered, which led to temporary myelosuppression. Recent examination showed that best corrected visual acuity was 20/400 OD. Fundoscopy showed petechial and patchy intra-retinal hemorrhage in both eyes and grayish-white lesion in the right macular center, which was confirmed as macular CNV by OCT and OCTA. DIAGNOSES: The patient was diagnosed as macular CNV OD related to AML and chemotherapeutic regimens. INTERVENTIONS: She received intravitreal ranibizumab injection 0.5 mg (10 mg/ml) in the right eye for once on January 3, 2017. OUTCOMES: CNV resolved three days after treatment with intravitreal ranibizumab injection 0.5 mg for once. No recurrence was observed after 10-month follow-up. Vision recovered to 20/40 at the last visit. LESSONS: This is the first report demonstrating that macular CNV could be an ophthalmic side-effect secondary to initiated chemotherapeutic regimens in patients with M3 AML. Intravitreal injection of ranibizumab could be beneficial and safe in treating this CNV.