Topical Clonidine Accelerates Cutaneous Wound Healing in Diabetic Rats by Regulating the Expression of Related Cytokine Signaling.

Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by regulating the expression of related cytokines. In this study, the wound healing effect of clonidine was evaluated using an excision wound model in diabetic rats and a HaCaT cell model. The wounds were treated daily with topical clonidine. The results analyzed by ImageJ2 software show that the wounds of the rats that were treated with 15 ng/mL clonidine recovered faster, and the wound size was also significantly reduced compared to the control group. Western blot assays determined that clonidine induced an increase in the expression of vascular growth factors, namely, Ang-1, Ang-2, and VEGF. Moreover, clonidine demonstrated a rescuing effect on JAK2 within the JAK/STAT pathway by inhibiting SOCS3 expression, leading to decreased SOCS3 levels and increased expression of JAK2 and phospho-STAT3. Histopathological analysis revealed that clonidine promoted complete epithelial repair and minimized inflammation in skin tissue. Additionally, clonidine stimulated HaCaT cell proliferation in vitro and enhanced cellular energy levels in the presence of AGEs. In conclusion, clonidine promoted vascular growth and wound healing by stimulating the expression of cytokines that are beneficial for wound healing.

Orf Infection on the Scalp of a Taiwanese Woman: A Case Report and Literature Review.

BACKGROUND: Orf, or ecthyma contagiosum, is a zoonosis caused by Parapoxvirus that infects sheep and goats. Human transmission typically occurs in persons in contact with the infected animals or contaminated fomites and environment. In humans, it generally occurs as solitary or multiple skin lesions on the hands or fingers. Involvement of the head region has rarely been reported. CASE PRESENTATION: We report an unusual case with multiple orf lesions on the scalp of a middle-aged woman, along with a review of previously reported Orf cases on the head region. CONCLUSIONS: Although Orf infection rarely happens on the head region, it should be considered in the differential diagnosis of cases with relevant animal exposure.

Using temporal heatmaps to identify worthwhile articles on immune checkpoint blockade for melanoma (ICBM) in Mainland China, Hong Kong, and Taiwan since 2000: A bibliometric analysis.

BACKGROUND: Melanoma is a life-threatening form of skin cancer. Due to its remarkable effectiveness, the immune checkpoint blockade is widely used to treat melanoma (ICBM). No research has been conducted on ICBM for identifying the most readable articles. A bibliometric analysis of 100 top-cited ICBM (T100ICBM) in recent decades is required to highlight articles worth reading. METHODS: Based on the Web of Science Core Collection, we summarized the articles on ICBM published in each year from 2000 to 2022, with first authors from Mainland China, Hong Kong, and Taiwan (CHT). Using the CJAL score, data extraction and visualization of the distribution of ICBM publications were conducted on 2718, and 100 top-cited articles, respectively. We used the temporal heatmap to identify the most readable articles. Four descriptive, diagnostic, predictive, and prescriptive analytics (called DDPP model) were applied to describe the features of T100ICBM articles. The absolute advantage coefficient was used to determine the dominance extent of the most influential region, institute, department, and author. RESULTS: A total of 2718 publications was included after removing first or corresponding authors who were not affiliated with CHT. Publications by year showed a sharp increase from 2014 onward and either peaked in 2022 or have not yet peaked. It was evident that there was a large difference between the number of publications in provinces/metropolitan cities/regions on CHT. Beijing, Sichuan University, Oncology, and Guo Jun from Beijing are the most prolific and influential region, institute, department, and author. When comparing research achievements to the next productive authors based on the CJAL score, only Dr Jun has a medium effect of dominance (=0.60). On the basis of their consecutive growth in citations over the past 4 years, 20 T100ICBM articles were recommended for readers. CONCLUSION: The field of ICBM is growing rapidly, and Beijing and Sichuan University are taking the lead in CHT. Furthermore, the study provides references for worth-reading articles using the temporal heatmap. Future research hot spots may focus on these 4 themes of immunotherapy, melanoma, metastatic melanoma, regulatory T cells, cells, and activation, which may pave the way for additional study.

Panfolliculoma: Report of the Youngest Case and Literature Review of Its Histopathologic Variants.

Background: Panfolliculoma (PF) is a relative rare, benign follicular tumor comprised of all elements of the hair follicle, with a limited number of cases reported in the literature. Articles on the demographic and pathological analysis of this tumor are also lacking. Case presentation: In this report, we presented an unusual case of cystic PF on the back of a 14-year-old male, and we performed a thorough literature review and analysis of all previously reported cases. Conclusions: PF is a rare benign follicular neoplasm with characteristic differentiation toward all components of the hair follicle. In our analysis, PF occurred most frequently on the head region and was usually diagnosed in middle- to old-aged persons, with cystic PF being the most common histologic subtype. Since this tumor is rare and easily misdiagnosed as other tumors both clinically and pathologically, a thorough understanding of the histopathological manifestations and differential diagnosis of this tumor is necessary for both dermatologists and pathologists.

Asymptomatic bacteriuria among the elderly residents of long-term care facilities in Taiwan.

BACKGROUND: asymptomatic bacteriuria (ASB) is common among the institutionalised elderly (IE). The cytokine levels and factors associated with ASB are unknown. OBJECTIVE: to analyse cytokines and factors associated with ASB among the IE living in long-term care facilities (LTCFs) in Taiwan. METHODS: this case-control study included residents ≥65 years in two LTCFs. The demographics, functional status, serum and urine levels of cytokines and proteins were compared between IE with ASB and those with sterile urine. Logistic regression was used to determine the factors associated with ASB. RESULTS: the IE with ASB had elevated IL-8 in blood and urine compared with the IE with sterile urine. The Barthel index score, serum creatinine, blood IL-8 and tumour necrosis factor-α levels were significant factors associated with ASB among the IE [odds ratio (OR) 0.957, 95% CI: 0.936-0.979, P < 0.0001; OR: 0.264, 95% CI: 0.076-0.912, P = 0.035 and OR: 1.088, 95% CI: 1.022-1.158, P = 0.009; OR: 0.828, 95% CI: 0.711-0.965, P = 0.016, respectively). CONCLUSION: functional status, renal function and blood cytokine levels were factors significantly associated with ASB among the IE living in Taiwan.

Breast cancers detected by breast MRI screening and ultrasound in asymptomatic Asian women: 8 years of experience in Taiwan.

BACKGROUND: This study investigated one-stop breast screening combining magnetic resonance imaging (MRI) and ultrasound (US) in asymptomatic Asian women. METHODS: 3,586 asymptomatic women (mean age, 45.3 years) were retrospectively analyzed by breast MRI followed by US. US-guided biopsy was performed when the MRI-detected lesion was confirmed by US. When the lesion was not detected on the initial US, a second-look US guided by MRI findings was performed. Then biopsy was done. MRI-positive and US-negative patients were followed up according to MRI lesion size, MRI lesion morphology, and mammographic diagnosis. RESULTS: In total, 115 subjects had suspicious malignant lesions and received US-guided biopsy, and 47 malignant lesions, including 35 invasive cancers and 12 carcinoma in situ (CIS) lesions, were diagnosed. More than half (22/35, 63%) of the women with invasive cancer were <50 years of age, and 27 (57.4%) of the 47 cancer cases had early breast cancers. Two invasive cancers (5.7%) and 7 CIS lesions (58.3%) were found at the second-look US. The overall cancer incidence was 1.31% (47/3,586) and increased to 2.2% (78/3,586) if precancerous lesions were included. Subjects aged 41-50 years had the highest incidence of cancer detection (1.97%). Five MRI and US-negative cases had cancers found 1 year after the screening. CONCLUSIONS: The results from the one-stop breast screening in this study showed that combining MRI and US is an efficient multimodality tool for screening asymptomatic Asian women in a metropolitan area of Taiwan who had concerns about the diagnosis and radiation of mammography.

Peroxisome proliferator-activated receptor delta agonists attenuated the C-reactive protein-induced pro-inflammation in cardiomyocytes and H9c2 cardiomyoblasts.

C-reactive protein (CRP) has emerged as a new marker for cardiovascular diseases. Activation of peroxisome proliferator-activated receptor delta (PPARdelta) plays beneficial roles in cardiac disorders. However, the relationship between CRP and PPARdelta in cardiac cells remains unclear. This study focused on the underlying molecular mechanisms of CRP and PPARdeltaagonists. Cardiomyocytes and cardiomyoblast cell line (H9c2) were used in different groups: Untreated; 15 microg/ml CRP with or without 1 microM PPARdelta agonists (L-165041). CRP increased PPARdelta and interleukin-6 expression in cardiomyocytes and H9c2 cardiomyoblasts. NF-kappaB inducing kinase (NIK) and NF-kappaB pathway also activated by CRP stimulation. These changes could be inhibited by L-165041 through p38MAPK and c-JNK pathways. However, transfection with siRNA of CD32 CRP receptor did not decrease CRP signaling or reverse the effects of L-165041 in CRP-treated cardiomyocytes and H9c2. Pretreatment with L-165041 attenuated apoptosis induced by hypoxia with or without CRP in H9c2 cardiomyoblasts. CRP up-regulated PPARdelta expression in cardiomyocytes and H9c2. L-165041 attenuated CRP-induced pro-inflammatory signaling through p38MAPK and c-JNK in H9c2 cardiomyoblasts. However, PPARdelta activation attenuated CRP-induced NF-kappaB pathway may be independent of CD32. These results may provide new evidence of PPARdelta beneficial effects for inflammatory cardiomyopathy.

Advanced glycation end products-induced apoptosis attenuated by PPARdelta activation and epigallocatechin gallate through NF-kappaB pathway in human embryonic kidney cells and human mesangial cells.

BACKGROUND: Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor delta (PPARdelta) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). METHODS: The HEK cells and HMC were separated into the following groups: 100 microg/mL AGE alone for 18 h; AGE treated with 1 microM L-165041 or 10 microM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-kappaB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. RESULTS: AGE significantly increased tumour necrosis factor-alpha (TNF-alpha), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pre-treatment with L-165041 or EGCG. AGE-induced nuclear factor-kappaB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. CONCLUSIONS: This study demonstrated that PPARdelta agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARdelta agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy.

Metabolic characteristics of breakfast-vegetarian (BV) elderly people in rural Taiwan.

Breakfast-vegetarianism (BV) is a special dietary habit in Chinese society, which is related to religious beliefs rather than health concerns. The purpose of this study was to compare metabolic characteristics of community-living middle-aged and elderly BV and non-vegetarians (NVs) in Taiwan. In 2000, people aged over 40 in I-Lan County were invited for study. In total, 367 people (mean age: 62.0+/-11.2 years, 57.8% female) participated in this study and 68 of them were BV. The BV subjects were less likely to consume oily food (29.4% vs. 43.1%, p=0.025), to smoke (5.9% vs. 23.1%, p<0.001) and to habitually consume alcohol (2.9% vs. 19.1%, p<0.001). Compared with NVs, the BVs were more prone to be females (86.8% vs. 44.7%, p<0.001), having lower glomerular filtration rate (GFR) (64.5+/-13.7 vs. 69.9+/-14.6ml/(kgmin), p=0.006), higher prevalence of metabolic syndrome (69.1% vs. 45.8%, p<0.001) and chronic kidney disease (CKD) (44.1% vs. 22.7%, p<0.001). By using logistic regression, females and chronic kidney disease were independently associated with the breakfast-vegetarianism. In conclusion, Taiwanese BVs seemed to lead a healthier life, but their metabolic characteristics were not significantly different from the NVs. Outcome study is needed to clarify the impact of BV habits on health.

Comparison of PPARδ and PPARγ in inhibiting the pro-inflammatory effects of C-reactive protein in endothelial cells.

BACKGROUND: Inflammation associated with endothelial cell dysfunction is a key step of atherogenesis. C-reactive protein (CRP), used to serve as a nonspecific clinical inflammation marker, has now emerged as a new marker for cardiovascular diseases. Recently, PPARδ has revealed benefits for dealing with inflammation. The relationship between CRP-induced inflammation and PPARδ agonist remains unclear. METHODS: Human umbilical vein endothelial cells (HUVECs) were separated into the following groups: 25 µg CRP alone for 15 hours; CRP-treated with 1 µM PPARδ(L-165041) or 10 µM PPARγ(troglitazone) agonists, and untreated HUVECs. This research focused on the CRP underlying signaling pathways and the effects of PPAR agonists on monocyte attachment to endothelial cells. RESULTS: Levels of interleukin-6 (IL-6) and IL-8 increased by CRP were both significantly attenuated by pretreatment with PPARδ or PPARγ agonists, but the needed dose of PPARδ to reach the same effect was less than PPARγ agonist. After incubation with CRP, immunoblotting showed a significant increase in NF-κB activation and CD32 receptor. These changes were associated with a significant increase of MCP-1 and VCAM-1 expression. PPARδ treatment not only decreased these pro-inflammatory effects in HUVECs but also significantly attenuated monocyte adhesion to endothelial cells in less dosage than PPARγ. CONCLUSIONS: The results suggest that PPARδ attenuated CRP-induced pro-inflammatory effects may through CD32 and NF-κB pathway. PPARδ may serve as a more potent therapeutic target than PPARγ in atherosclerosis or inflammatory therapy.

Mechanical stress enhances serotonin 2B receptor modulating brain natriuretic peptide through nuclear factor-kappaB in cardiomyocytes.

OBJECTIVE: Serotonin via serotonin 2B receptors (SR2BR) regulates cardiac embryonic development and adult heart functions. However, the role of SR2BR in the failing heart due to pressure overload is not well understood. METHODS: Wistar rats of aortic banding and neonatal cardiomyocyte with mechanical stretch were used as cardiomyopathy models. RESULTS: After two weeks of aortic banding surgery, serum serotonin, mRNA and protein expression of SR2BR increased significantly. The selective SR2BR antagonist, SB215505 (SB), significantly reduced the increase in heart weight, decreased heart wall thickness, left ventricular mass and the expression of the brain natriuretic peptide (BNP) but did not attenuate the up-regulation of SR2BR protein expression in rats after aortic banding for three weeks. After following in vitro mechanical stretch of cardiomyocytes and incubation with serotonin 1 muM, the level of SR2BR and BNP protein increased time-dependently. When transfected by specific siRNA of SR2BR or pretreated with caffeic acid phenethyl ester in cardiomyocytes, the increase of nuclear factor-kappaB (NF-kappaB) translocation and BNP protein induced by serotonin incubation plus mechanical stretch were both reversed. CONCLUSIONS: SR2BR expression is involved in pressure-induced cardiomyopathy and its downstream signaling may involve NF-kappaB to modulate BNP expression in cardiomyocyte.