Facial Merkel cell carcinoma in a patient with diabetes and hepatitis B: A case report.

BACKGROUND: Patients with chronic inflammatory disorders are at a higher risk of developing aggressive Merkel cell carcinoma (MCC). Diabetes is a common chronic inflammatory disease that is possibly associated with MCC; however, there are still no reports on the association between hepatitis B virus (HBV) infection and MCC. Whether there is an association between these three diseases and the specific mechanisms behind their effects is worth further research in the future. CASE SUMMARY: We herein report a rare case of MCC with extracutaneous and nodal invasion in an Asian individual with type 2 diabetes mellitus and chronic HBV infection, but no immunosuppression or other malignancies. Such cases are uncommon and have rarely been reported in the literature. A 56-year-old Asian male presented with a significant mass on his right cheek and underwent extensive resection combined with parotidectomy, neck lymphadenectomy, and split-thickness skin grafting. Based on the histopathological findings, a diagnosis of MCC involving the adipose tissue, muscle, nerve, and parotid gland with lymphovascular invasion was made. Subsequently, he received radiotherapy with no adverse reactions. CONCLUSION: MCC is a rare, aggressive skin cancer with frequent local recurrence, nodal invasion, and metastasis, which usually arises in older people of the white race. Patients with chronic inflammatory disorders are at a higher risk of developing aggressive MCC. The diagnosis can be confirmed with histology and immunohistochemistry. For localized MCC, surgery is the preferred treatment option. However, for advanced MCC, radiotherapy and chemotherapy have proven to be effective. In cases where chemotherapy is not effective or in the advanced stages of MCC, immune therapy plays an important role in treatment. As with any rare disease, the management of MCC remains an enormous challenge for clinicians; thus, follow-up should be individualized and future progress needs multidisciplinary collaborative efforts. Furthermore, physicians should include MCC in their list of possible diagnoses when they come across painless, rapidly growing lesions, particularly in patients with chronic HBV infection or diabetes, as these patients are more susceptible to the development of this condition and it tends to be more aggressive in them.

Effective decolonization strategy for mupirocin-resistant Staphylococcus aureus by TPGS-modified mupirocin-silver complex.

The widespread utilization of mupirocin to treat methicillin-resistant Staphylococcus aureus (MRSA)-caused infectious diseases has led to the emergence of mupirocin-resistant Staphylococcus aureus (MuRSA), posing a serious global medical threat. In order to counteract MuRSA, we develop a d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified mupirocin and silver complex (TPGS/Mup-Ag) to combat MuRSA. The surfactivity of TPGS endows Mup-Ag with a homogeneous and small particle size (∼16 â€‹nm), which significantly enhances bacterial internalization. Silver ions are released from the mupirocin-Ag complex (Mup-Ag) to exert a synergistic antibacterial activity with mupirocin. Results manifest that our strategy reduces the concentration of mupirocin that induces 50% bacterial death from about 1000 â€‹µmol/mL to about 16 â€‹µmol/mL. In vitro bacterial infection model suggests that TPGS/Mup-Ag can not only eliminate both intracellular and inhibit bacterial adhesion, but also living cells are not affected. Results of in vivo experiments demonstrate that TPGS/Mup-Ag can effectively inhibit the progression of skin infection and accelerate wound healing, as well as alleviate systemic inflammation in both the subcutaneous infection model and the wound infection model. Furthermore, this study may contribute to the development of therapeutic agents for antibiotic-resistant bacteria and offer ideas for silver-based bactericides.

Crosstalk between oncolytic viruses and autophagy in cancer therapy.

Oncolytic viruses have attracted attention as a promising strategy in cancer therapy owing to their ability to selectively infect and kill tumor cells, without affecting healthy cells. They also exert their anti-tumor effects by releasing immunostimulatory molecules from dying cancer cells. Several regulatory mechanisms, such as autophagy, contribute to the anti-tumor properties of oncolytic viruses. Autophagy is a conserved catabolic process in responses to various stresses, such as nutrient deprivation, hypoxia, and infection that produces energy by lysosomal degradation of intracellular contents. Autophagy can support infectivity and replication of the oncolytic virus and enhance their anti-tumor effects via mediating oncolysis, autophagic cell death, and immunogenic cell death. On the other hand, autophagy can reduce the cytotoxicity of oncolytic viruses by providing survival nutrients for tumor cells. In his review, we summarize various types of oncolytic viruses in clinical trials, their mechanism of action, and autophagy machinery. Furthermore, we precisely discuss the interaction between oncolytic viruses and autophagy in cancer therapy and their combinational effects on tumor cells.

HOG1 has an essential role in the stress response, virulence and pathogenicity of Cryptococcus gattii.

Cryptococcus gattii (C. gattii) is a lethal pathogen that causes the majority of cryptococcosis cases in previously healthy individuals. This pathogen poses an increasing threat to global public health, but the mechanisms underlying the pathogenesis have remained to be fully elucidated. In the present study, the role of high-osmolarity glycerol (HOG)1 in the stress reaction and virulence control of C. gattii was characterized by deleting the HOG1 gene using the clinical isolate strain CZ2012, and finally, the virulence and pathogenic traits of the deletion strain were defined. Deletion of the HOG1 gene resulted in notable growth defects under stress conditions (high salt and antifungal drugs), but different traits were observed under oxidative stress conditions (hydrogen peroxide). Similarly, the C. gattii hog1Δ strains (deletion of HOG1) also displayed decreased capsule production and melanin synthesis. Furthermore, mice infected with the hog1Δ strain had longer survival times than those infected with the wild-type strain and the reconstituted strain. The hog1Δ strain recovered from infected organs exhibited significant growth defects in terms of decreased colony count and size. The present results suggested that HOG1 has a significant role in the virulence of C. gattii and these results may help to elucidate the pathogenesis of C. gattii.

Melatonin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-related Diseases.

Cartilage is a relatively simple connective tissue that plays a variety of roles in the human body, including joint support and protection, load bearing of the intervertebral discs, joint lubrication, formation of the external structure of the ears and nose and support of the trachea. The maintenance of cartilage homeostasis is therefore crucial. Cartilage-related diseases are difficult to diagnose and treat because their molecular and pathological mechanisms are not fully understood. Melatonin, which has a wide range of physiological effects, is an endocrine hormone mainly secreted by the pineal gland. Its biological effects include its antioxidant, antiaging, analgesic, and hypnotic effects and its ability to stabilize the circadian rhythm. In recent years, research on cartilage homeostasis and melatonin has been increasing, and melatonin has gradually been used in the treatment of cartilage-related diseases. Therefore, this article will briefly review the role of melatonin in cartilage homeostasis, including its anti-inflammatory effects and effects in protecting cartilage from damage by other factors and promoting chondrocyte growth and the expression of cartilage-related genes. Based on the above, the current status and future developmental direction of melatonin in the treatment of cartilage-related diseases are also discussed, demonstrating the broad prospects of melatonin in maintaining cartilage homeostasis and treating cartilage injury-related diseases.

Mitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions.

Sarcopenia is a common geriatric disorder characterized by decreased muscle strength, low muscle mass and poor physical performance. This aging-related skeletal muscle deterioration leads to adverse outcomes and severely impairs the quality of life of patients. The accumulation of dysfunctional mitochondria with aging is an important factor in the occurrence and progression of sarcopenia. Mitochondrial quality control (MQC) fundamentally ensures the normal mitochondrial functions and is comprised of four main parts: proteostasis, biogenesis, dynamics and autophagy. Therefore, any pathophysiologic factors compromising the quality control of homeostasis in the skeletal muscle may lead to sarcopenia. However, the specific theoretical aspects of these processes have not been fully elucidated. Current therapeutic interventions using nutritional and pharmaceutical treatments show a modest therapeutic efficacy; however, only physical exercise is recommended as the first-line therapy for sarcopenia, which can ameliorate skeletal muscle deficiency by maintaining the homeostatic MQC. In this review, we summarized the known mechanisms that contribute to the pathogenesis of sarcopenia by impairing normal mitochondrial functions and described potential interventions that mitigate sarcopenia through improving MQC.

Surface Engineered Metal-Organic Frameworks (MOFs) Based Novel Hybrid Systems for Effective Wound Healing: A Review of Recent Developments.

Wounds present serious medical complications and their healing requires strategies that promote angiogenesis, deposition of collagen as well as re-epithelialization of wounds. Currently used conventional wound healing strategies have become less effective due to various issues associated with them. Thus, novel strategies are needed to be developed for early and effective healing of wounds. Metal-organic frameworks (MOFs), formed by linking of metal ions through organic bridging ligands, are highly tunable hybrid materials and have attracted more considerable scientific attention due to their charming and prominent properties, such as abundant pore structures and multiple functionalities. Surface engineering of MOFs with unique ligands can overcome issues associated with conventional wound healing methods, thus resulting in early and effective wound healing. This review has been undertaken to elaborate wound healing, and the use of surface engineered MOFs for effective and rapid wound healing. The process of wound healing will be discussed followed by a detailed review of recent literature for summarizing applications of surface engineered MOFs for wound healing. MOFs wound healing will be discussed in terms of their use as antibacterial agents, therapeutic delivery vehicles, and dressing systems in wound healing.

Tibetan medicine Ru-yi-Zhen-bao Pills exhibits anti-migraine effect through mediating PAG anti-nociceptive channel.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is a disabling neurovascular disorder, which increases risk of cardiovascular events and is a social burden worldwide. The present first-line anti-migraine medications can cause overwhelming side-effects, of which one includes the onset of cardiovascular disease. As one of the marketed Tibetan drugs, Ru-yi-Zhen-bao Pills (RYZBP) have been clinically used to treat cardiovascular disorders and as anti-migraine medication. However, there is currently no research exploring the anti-migraine actions of RYZBP. AIM OF THE STUDY: The current research was designed to assess the anti-migraine roles of RYZBP and explore the underlying mechanisms in a nitroglycerin (NTG)-induced migraine rat model trial. MATERIALS AND METHODS: 120 rats were randomly divided into the following six groups of 20 rats each: normal control group, model control group, positive control group, and RYZBP high/medium/low-dose groups (Ru-yi-Zhen-bao Pills; TH 1.00 g/kg, TM 0.50 g/kg and TL 0.25 g/kg). All rats were administered intragastrically for 7 consecutive days, which were subcutaneously injected with the NTG (10 mg/kg) after the last gavage (except in the normal control group). 3min after NTG treatment, 30 rats (5 rats from each group) were anesthetized and devoted to electroencephalogram(EEG) testing, which was used to evaluate the analgesic effect of RYZBP. One hour after NTG treatment, the rest of the 90 rats (15 rats from each group) were anesthetized and midbrain tissue sample was dissected. The dissection was then washed with physiological saline and collected. The histopathological changes in the periaqueductal gray(PAG) of 5 tissue samples were determined by aematoxylin-eosin (H&E) staining, as well as an estimation of substance P (SP) and neurokinin 1 receptor (NK1R) expression through immunohistochemically staining(IHC). Another 5 midbrain preparations were carried out to evaluate calcitonin gene-related peptide (CGRP), proenkephalin (PENK), SP, and cholecystokinin (CCK) expressions by real-time quantitative polymerase chain reaction (RT-qPCR). The rest of the 5 brainstem tissues were then used to measure CCK, CGRP, and opioid peptide receptor (DORR) levels by western blotting(WB). RESULTS: In the EEG test, RYZBP (TM 0.50 g / kg) treatment transformed the EEG pain-wave of the NTG-induced migraine model rats in different time period. In the mechanism assay, compared with the model control group, RYZBP pretreatment reduced inflammatory cell infiltration, fibrosis and vacuolation of neuronal cells of PAG tissue seen by HE staining. IHC experiments further showed that RYZBPTM up-regulated SP expression levels and enhanced NK1R levels in the NTG-induced migraine rats (P < 0.05). Therapeutic administration of RYZBP also increased PENK mRNA expression and DORR protein level. Both RT-qPCR and western blotting trials indicated that RYZBP treatment significantly decreased CCK and CGRP expression levels (P < 0.01 or P < 0.05) in the NTG-induced migraine rats. CONCLUSIONS: RYZBP has the potential to be an effective anti-migraine treatment through suppressing the EEG pain-wave, increasing the levels of SP, PENK, DORR and reducing expression of CCK and CGRP. Mediating the PAG anti-nociceptive channel and inhibiting central sensitization were the two potential mechanisms, which offers further evidence for clinical therapy.

Significance of SHP-1 and SHP-2 expression in human papillomavirus infected Condyloma acuminatum and cervical cancer.

Human papillomaviruses (HPVs) are a group of DNA viruses that infect the skin and mucous membranes. Type HPV6/11 is closely related to Condyloma acuminatum, while HPV16/18 is the principal cause of cervical cancer. In this study, we examined the expression of protein tyrosine phosphatases SHP-1 and SHP-2 in Condyloma acuminatum, cervical cancer and the relationship between SHP-1/SHP2 expression and HPV infection. Forty Condyloma acuminatum cases, 20 cervical cancer cases and 20 normal human foreskins were examined for HPV infection by in situ hybridization and the expression of SHP-1 and SHP-2 were examined by immunohistochemistry. Results demonstrated that positive expression rates of HPV6/11, HPV16/18, and HPV31/33 were 98%, 10%, and 7.5% in Condyloma acuminatum, 10%, 85%, and 25% in cervical cancer. Only one normal foreskin demonstrated positive staining for HPV16/18. Positive expression rates of SHP-1 and SHP-2 were 80% and 85% in Condyloma acuminatum, 85% and 90% in cervical cancer. The SHP-1 and SHP-2 expressions were mainly distributed in the prickle layer of Condyloma acuminatum and were diffusely distributed in cervical cancer cells. Only 35% and 30% of foreskins demonstrated weak staining in the basal layer cells. There were statistically significant correlations among the infection of HPV and the expression of SHP-1 and SHP-2 in both Condyloma acuminatum and cervical cancer (P < 0.05). SHP-1 expression has a positive correlation with SHP-2 expression. Our results demonstrate putative roles of SHP-1 and SHP-2 in the progression of both Condyloma acuminatum and cervical cancer after HPV infection.

[Comparative proteome analysis of human papillomavirus-infected cervical specimens and the difference between the high- and low-risk genotypes of human papillomavirus].

OBJECTIVE: To perform an comparative proteome analysis of human papillomavirus-infected cervical specimens and to investigate different expressions between high- and low-risk genotypes. METHODS: The cervical specimens were divided into two groups (cervical intraepithelial neoplasia group and condyloma acuminatum group) according to their genotypes. Using comparative proteome technology, high-risk human papillomavirus-infected cervical intraepithelial neoplasia, low-risk human papillomavirus-infected condyloma acuminatum, and normal cervical intraepithelial tissue were compared. The differential expression protein spots were identified by mass spectrometry. RESULTS: Totally 26 differential spots were selected and analyzed, and 22 peptide mass fingerprints (PMF) maps were obtained by MALDI-TOF-MS. Eighteen proteins were preliminarily identified after searching the NCBInr database. The function information of these 18 proteins mainly involved cell metabolism, signal transduction, cell secretion, cell cytoskeleton construction, cell proliferation, and apoptosis. CONCLUSION: The proteomic expressions after the cervical infection of high- or low-risk genotype of human papillomavirus are obviously different.

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model.

AIM: To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS: Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-mum thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS: The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, P<0.01) and pressure (11.014+/-0.395 vs 8.533+/-0.274 mmHg, P<0.01) of portal vein were significantly higher in model group than those in the control group. Plasma HA (129.97+/-16.10 vs 73.09+/-2.38 ng/mL, P<0.01), ColIV (210.49+/-4.36 vs 89.65+/-4.42 ng/mL, P<0.01) and LN (105.00+/-7.29 vs 55.70+/-4.32 ng/mL, P<0.01) were upregulated in model group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased remarkably and perisinusoids were almost surrounded by ColIII. Immunohistochemical staining showed that ColIV protein level (0.130+/-0.007 vs 0.032+/-0.004, P<0.01) and LN protein level (0.152+/-0.005 vs 0.029+/-0.005, P<0.01) were up-regulated remarkably in model group. MMP-2 protein expression (2.306+/-1.089 vs 0.612+/-0.081, P<0.01) and TIMP-1 protein expression (3.015+/-1.364 vs 0.446+/-0.009, P<0.01) in freshly isolated hepatic non-parenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, P<0.05). CONCLUSION: Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcohol-induced portal hypertension in rats.

High prevalence of syphilis among street-based female sex workers in Nanchang, China.

BACKGROUND: Female sex workers (FSWs) play a critical role in the heterosexual transmission of human immunodeficiency virus (HIV)/sexually transmitted infections (STIs) in China. Several studies reported that street-based FSWs have higher risk behaviors than establishment-based FSWs. Therefore, street-based FSWs should be specifically targeted for HIV and STIs intervention programs. OBJECTIVES: This study aims to investigate the prevalence rates and risk factors of HIV and syphilis among FSWs in Nanchang, China. MATERIALS AND METHODS: Using convenience sampling methods, 361 street-based FSWs were recruited from August 2011 to February 2012. All participants completed an anonymous questionnaire on socioeconomic and sex behavioral information and were tested for HIV and syphilis. Risk for HIV and syphilis infection was assessed using univariate and multivariate logistic regression analyses. RESULTS: No HIV infections were found. The prevalence rate of syphilis was 43.5%. Nearly 46.1% of street-based FSWs reported having education for no more than 6 years. Having reproductive tract infections at current visit, duration of sex work more than 5 years, indulgence in unprotected sex trade in the last time, unprotected sex trade in the last month, and unprotected sex with boyfriend or spouse in the last month were reported by 35.2%, 43.5%, 33.8%, 60.4%, and 93.1% street-based FSWs, respectively. In multivariate logistic regression analysis, having reproductive tract infections at current visit [odds ratio (OR), 12.10; 95% confidence interval (CI), 6.01-24.37], duration of sex work more than five years (OR, 4.26; 95% CI, 2.40-7.54), and unprotected sex trade in the last month (OR, 1.85; 95% CI, 1.06-3.22) were independently associated with syphilis infection. CONCLUSION: The prevalence rate of syphilis among street-based FSWs is very high. Most street-based FSWs in our survey had low education, long experience of commercial sex, and high rate of inconsistent condom use. Comprehensive interventions targeting this high-risk group, especially scaling up screening and ensuring consistent use of condoms during sex are needed.

Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia: a systemic review.

BACKGROUND: The current treatment of cervical intraepithelial neoplasia (CIN) is primarily based on surgical excision using laser, a loop electrosurgical procedure, or a cold knife technique. Unfortunately, these treatments often lead to obstetrical problems during the subsequent pregnancy, particularly in young women. Photodynamic therapy (PDT), which uses a topical or intravenous photosensitizer (PS) activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to comprehensively assess the effectiveness and safety of PDT in the treatment of CIN. METHODS: Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for CIN was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale. RESULTS: The 14 studies included two randomized control trials (RCTs), one case-control study, and 11 case series. Among the 506 patients studied, 472 were included to study the effectiveness of PDT on CIN and 10 were lost to follow-up. An assessment of clinical effectiveness included the response of the lesion to treatment (may include lesion recurrence) reported by all 14 studies. The complete response rate (CRR) of PDT on CIN ranged from 0% to 100%. HPV eradication rate (HER) was reported in seven studies, with rates ranging from 53.4% to 80.0%. CONCLUSIONS: PDT is a safe and tolerable treatment for CIN. Evidence regarding the efficacy of PDT for CIN is conflicting, which may, in part, be explained by the limited number of controlled comparative clinical trials.