Yeqiang Liu

Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice

Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion (I/R) injury. Interleukin (IL)‐37 is a newly identified member of the IL‐1 family, and functions as a fundamental inhibitor of innate immunity and inflammation. However, its role in myocardial I/R injury remains unknown. I/R or sham operations were performed on male C57BL/6J mice. I/R mice received an injection of recombinant human IL‐37 or vehicle, immediately before reperfusion. Compared with vehicle treatment, mice treated with IL‐37 showed an obvious amelioration of the I/R injury, as demonstrated by reduced infarct size, decreased cardiac troponin T level and improved cardiac function. This protective effect was associated with the ability of IL‐37 to suppress production of proinflammatory cytokines, chemokines and neutrophil infiltration, which together contributed to a decrease in cardiomyocyte apoptosis and reactive oxygen species (ROS) generation. In addition, we found that IL‐37 inhibited the up‐regulation of Toll‐like receptor (TLR)‐4 expression and nuclear factor kappa B (NF‐kB) activation after I/R, while increasing the anti‐inflammatory IL‐10 level. Moreover, the administration of anti‐IL‐10R antibody abolished the protective effects of IL‐37 in I/R injury. In‐vitro experiments further demonstrated that IL‐37 protected cardiomyocytes from apoptosis under I/R condition, and suppressed the migration ability of neutrophils towards the chemokine LIX. In conclusion, IL‐37 plays a protective role against mouse myocardial I/R injury, offering a promising therapeutic medium for myocardial I/R injury.

Gambogic acid induces apoptosis by regulating the expression of Bax and Bcl‐2 and enhancing caspase‐3 activity in human malignant melanoma A375 cells

Objectives  To investigate the effect of a Chinese traditional medicine, gambogic acid (GA), on human malignant melanoma (MM) A375 cells and to study the mechanism of apoptosis induced by GA.

An outbreak of 268 cases of Paederus dermatitis in a toy‐building factory in central China

Objective  To evaluate the clinical features of and to identify the pathogen responsible for an outbreak of acute dermatitis in a toy‐building factory in Chibi city, central China.

Targeting Hypoxia-inducible Factor-1α With Tf–PEI–shRNA Complex via Transferrin Receptor–mediated Endocytosis Inhibits Melanoma Growth

Malignant melanoma (MM) is a major public health problem. The development of effective, systemic therapies for MM is highly desired. We showed here that the transferrin receptor (TfR) was a suitable surface marker for targeting of gene therapy in MM and that the hypoxia-inducible factor-1α (HIF-1α) was an attractive therapeutic molecular target in MM. We observed that inhibition of HIF-1α blocked cell proliferation and induced cell apoptosis in vitro. We then showed that a transferrin-polyethylenimine-HIF-1α-short-hairpin RNA (Tf-PEI-HIF-1α-shRNA) complex could target MM specifically and efficiently both in vivo and in vitro, exploiting the high expression of the TfR in MM. The systemic delivery of sequence-specific small-interfering RNA (siRNA) against HIF-1α by the Tf- PEI-HIF-1α-shRNA complex dramatically inhibited tumor growth in the A375 MM xenograft model. The underlying concept of transfecting a HIF-1α shRNA expression vector complexed with Tf-PEI to block HIF-1α holds promise as a clinical approach to gene therapy for MM.Malignant melanoma (MM) is a major public health problem. The development of effective, systemic therapies for MM is highly desired. We showed here that the transferrin receptor (TfR) was a suitable surface marker for targeting of gene therapy in MM and that the hypoxia-inducible factor-1alpha (HIF-1alpha) was an attractive therapeutic molecular target in MM. We observed that inhibition of HIF-1alpha blocked cell proliferation and induced cell apoptosis in vitro. We then showed that a transferrin-polyethylenimine-HIF-1alpha-short-hairpin RNA (Tf-PEI-HIF-1alpha-shRNA) complex could target MM specifically and efficiently both in vivo and in vitro, exploiting the high expression of the TfR in MM. The systemic delivery of sequence-specific small-interfering RNA (siRNA) against HIF-1alpha by the Tf- PEI-HIF-1alpha-shRNA complex dramatically inhibited tumor growth in the A375 MM xenograft model. The underlying concept of transfecting a HIF-1alpha shRNA expression vector complexed with Tf-PEI to block HIF-1alpha holds promise as a clinical approach to gene therapy for MM.

Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in human malignant melanoma and their relation to angiogenesis

Background.  Angiogenesis is the major and key factor for growth and invasion of tumours, including malignant melanoma (MM), but the factors that contribute to tumour angiogenesis are still unclear. 

The immunosuppressive and protective ability of glucose-regulated protein 78 for improvement of alloimmunity in β cell transplantation

An insulinoma cell line, NIT‐1, transfected with glucose‐regulated protein 78 (GRP78) was established, namely NIT‐GRP78, and used to study the immunosuppressive and protective ability of GRP78. In extended cytotoxic T lymphocyte (CTL) killing assay, NIT‐1‐primed lymphocytes were more cytotoxic in killing β cells than NIT‐GRP78‐primed lymphocytes. Severe necrosis was observed only when the NIT‐1‐primed lymphocytes were cultured with NIT‐1 β cells, but not with NIT‐GRP78 cells. In addition, an increase of interleukin (IL)‐4 secretion from β cell‐primed splenocytes when GRP78 presence was observed in cytokine enzyme‐linked immunosorbent assay (ELISA). Diabetic mice reached normoglycaemia promptly and gained weight after transplantation of either NIT‐1 or NIT‐GRP78 cells. However, the recipient mice transplanted with NIT‐GRP78 cells lived much longer than those recipients transplanted with NIT‐1 cells, which was due apparently to prolonged insulin production by the transplanted NIT‐GRP78 cells. In fact, we observed a significant increase of insulin concentration after glucose stimulation of diabetic mice received NIT‐GRP78 cells at day 7 post‐transplantation. From the results we propose that GRP78 could have a dual function in both protecting NIT‐1 cells from CTL‐mediated lysis and stimulating a population of T helper 2 cells to down‐regulate the immune response to the transplanted β cells.

Targeting hypoxia-inducible factor-1alpha with Tf-PEI-shRNA complex via transferrin receptor-mediated endocytosis inhibits melanoma growth.

Malignant melanoma (MM) is a major public health problem. The development of effective, systemic therapies for MM is highly desired. We showed here that the transferrin receptor (TfR) was a suitable surface marker for targeting of gene therapy in MM and that the hypoxia-inducible factor-1α (HIF-1α) was an attractive therapeutic molecular target in MM. We observed that inhibition of HIF-1α blocked cell proliferation and induced cell apoptosis in vitro. We then showed that a transferrin-polyethylenimine-HIF-1α-short-hairpin RNA (Tf-PEI-HIF-1α-shRNA) complex could target MM specifically and efficiently both in vivo and in vitro, exploiting the high expression of the TfR in MM. The systemic delivery of sequence-specific small-interfering RNA (siRNA) against HIF-1α by the Tf- PEI-HIF-1α-shRNA complex dramatically inhibited tumor growth in the A375 MM xenograft model. The underlying concept of transfecting a HIF-1α shRNA expression vector complexed with Tf-PEI to block HIF-1α holds promise as a clinical approach to gene therapy for MM.Malignant melanoma (MM) is a major public health problem. The development of effective, systemic therapies for MM is highly desired. We showed here that the transferrin receptor (TfR) was a suitable surface marker for targeting of gene therapy in MM and that the hypoxia-inducible factor-1alpha (HIF-1alpha) was an attractive therapeutic molecular target in MM. We observed that inhibition of HIF-1alpha blocked cell proliferation and induced cell apoptosis in vitro. We then showed that a transferrin-polyethylenimine-HIF-1alpha-short-hairpin RNA (Tf-PEI-HIF-1alpha-shRNA) complex could target MM specifically and efficiently both in vivo and in vitro, exploiting the high expression of the TfR in MM. The systemic delivery of sequence-specific small-interfering RNA (siRNA) against HIF-1alpha by the Tf- PEI-HIF-1alpha-shRNA complex dramatically inhibited tumor growth in the A375 MM xenograft model. The underlying concept of transfecting a HIF-1alpha shRNA expression vector complexed with Tf-PEI to block HIF-1alpha holds promise as a clinical approach to gene therapy for MM.

Olmsted syndrome: a case report and review of literature.

We report a case of an 18‐month‐old boy with slightly whitened fingernails and toenails since birth. At the age of 100 days, he progressively developed bilateral palmoplantar keratoderma which resulted in painful walking and disabled grasping. Perianal keratotic plaques and perioral hyperkeratotic erythema could also be observed. Both fingernails and toenails were dystrophic. Scalp hairs were sparse, but total alopecia was no present. The histopathologic changes of the biopsy from the inner side of the right foot showed nonspecific changes, which mainly showed highly hyperkeratosis and acanthosis with slight superficial perivascular inflammatory infiltration. A clinical diagnosis of Olmsted syndrome was established according to the typical feature of the lesions, which is the presence of symmetrical palmoplantar keratoderma with periorificial keratotic plaques. We review the literature and present a summary of all reported cases to date.

Expression of antiapoptotic protein c-FLIP is upregulated in psoriasis epidermis

The most characteristic change in psoriasis is markedly increased, persistent keratinocyte proliferation. The pathogenic mechanism underlying the hyperproliferation of keratinocytes in psoriasis is still not completely clarified. Cellular FLIP (cFLIP) is a close homologue of caspase 8 without the caspase activity that inhibits Fas signaling. The cFLIP protein is often expressed in human tumors and is believed to suppress antitumor immune responses involving the Fas system. PCNA is an auxiliary protein of DNA polymerase-5, which appears early in G1 and becomes more abundant in the S phase, thereafter declining during G2/M phases of the cell cycle. Thus, the PCNA staining profiles were used as markers of keratinocyte proliferation. Our objective was to obtain insight into the role of c-FLIP in kerarinocyte proliferation and to investigate further the pathogenesis of psoriasis. Using real time quantitative reverse transcriptase-polymerase chain reactions (RT-PCR) and immunohistochemical staining, we studied the expression of c-FLIP mRNA and protein in skin biopsies from psoriatic patients and healthy subjects. Apoptotic cells were evaluated using the terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. c-FLIP mRNA and protein expressions were significantly greater in lesional psoriatic epidermis compared with normal and non-lesional psoriatic epidermis (P < 0.01). c-FLIP was strongly expressed within all epidermal layers in lesional psoriatic skin, whereas weak c-FLIP staining was restricted to the basal and suprabasal layers in normal and non-lesional psoriatic epidermis. c-FLIP protein levels significantly correlated with PASI score, PCNA and apoptosis index (Spearmans rho = 0.83; rho = 0.61; rho = - 0.41; P < 0.05, respectively). We conclude that over-expression of c-FLIP in lesional psoriatic skin might contribute to abnormal keratinocyte proliferation due to a functional decrease in the apoptotic pathway.

Expression of transporters associated with antigen processing and human leucocyte antigen class I in malignant melanoma and its association with prognostic factors

Background  Low expression of transporters associated with antigen processing (TAP) and human leucocyte antigen (HLA) class I, due to defects in the antigen presentation pathway, is frequently found in human tumours, including malignant melanoma (MM). This immune evasion renders many tumours unrecognizable by the host immune surveillance system and appears to play a role in the clinical course of the tumour, probably because it provides tumour cells with a mechanism to escape cytotoxic T‐lymphocyte recognition and destruction. However, the histopathological significance of TAP and HLA class I antigen defects in MM remains unclear.