miRSNP rs188493331: A key player in genetic control of microRNA-induced pathway activation in hypertrophic scars and keloids.

BACKGROUND: Our study aims to delineate the miRSNP-microRNA-gene-pathway interactions in the context of hypertrophic scars (HS) and keloids. MATERIALS AND METHODS: We performed a computational biology study involving differential expression analysis to identify genes and their mRNAs in HS and keloid tissues compared to normal skin, identifying key hub genes and enriching their functional roles, comprehensively analyzing microRNA-target genes and related signaling pathways through bioinformatics, identifying MiRSNPs, and constructing a pathway-based network to illustrate miRSNP-miRNA-gene-signaling pathway interactions. RESULTS: Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-ß, PI3K/Akt, and EGFR tyrosine kinase inhibitor resistance. Particularly noteworthy was the substantial crosstalk between the focal adhesion and PI3K/Akt signaling pathways, making them more susceptible to regulation by microRNAs. We also identified specific miRNAs, including miRNA-1279, miRNA-429, and miRNA-302e, which harbored multiple SNP loci, with miRSNPs rs188493331 and rs78979933 exerting control over a significant number of miRNA target genes. Furthermore, we observed that miRSNP rs188493331 shared a location with microRNA302e, microRNA202a-3p, and microRNA20b-5p, and these three microRNAs collectively targeted the gene LAMA3, which is integral to the focal adhesion signaling pathway. CONCLUSIONS: The study successfully unveils the complex interactions between miRSNPs, miRNAs, genes, and signaling pathways, shedding light on the genetic factors contributing to HS and keloid formation.

Attenuated vaccine PmCQ2Δ4555-4580 effectively protects mice against Pasteurella multocida infection.

Pasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At present, there is still no effective commercial vaccine against PmA infection. In this study, a mutant strain (PmCQ2Δ4555-4580) with brand-new phenotypes was obtained after serially passaging at 42 °C. Whole genome resequencing and PCR analysis showed that PmCQ2Δ4555-4580 missed six genes, including PmCQ2_004555, PmCQ2_004560, PmCQ2_004565, PmCQ2_004570, PmCQ2_004575, and PmCQ2_004580. Importantly, the virulence of PmCQ2Δ4555-4580 was reduced by approximately 2.8 × 109 times in mice. Notably, live PmCQ2Δ4555-4580 could provide 100%, 100% and 40% protection against PmA, PmB and PmF, respectively; and inactivated PmCQ2Δ4555-4580 could provide 100% and 87.5% protection against PmA and PmB. Interestingly, immune protection-related proteins were significantly upregulated in PmCQ2Δ4555-4580 based on RNA-seq and bioinformatics analysis. Meaningfully, by in vitro expression, purification and in vivo immunization, 12 proteins had different degrees of immune protective effects. Among them, PmCQ2_008205, PmCQ2_010435, PmCQ2_008190, and PmCQ2_004170 had the best protective effect, the protection rates against PmA were 50%, 40%, 30%, and 30%, respectively, and the protective rates against PmB were 62.5%, 42.9%, 37.5%, and 28.6%, respectively. Collectively, PmCQ2Δ4555-4580 is a potential vaccine candidate for the prevention of Pasteurellosis involving in high expression of immune protective related proteins.

Isolation and Genomic Characterization of a Chinese Genotype C Bovine Parainfluenza Virus Type 3 from Cattle and Its Pathogenicity in C57BL/6 Mice.

Bovine parainfluenza virus type 3 (BPIV-3), also known as bovine respirovirus 3, is a common respiratory pathogen associated with bovine respiratory disease (BRD). BPIV-3 has currently circulated worldwide; however, data on the prevalence and genetic characteristics of BPIV-3 are still scarce and limited. In this study, the BPIV-3 strain SC was identified and isolated from cattle presenting with clinical signs of BRD in China. Animal experiments indicated that BPIV-3 SC can successfully infect C57BL/6 mice and induce weight loss, lung inflammatory cell infiltration, and inflammatory cytokine expression in mice. In addition, the complete genome of BPIV-3 SC was obtained using next-generation sequencing and was 15,473 bp in length. Phylogenetic analysis indicated that BPIV-3 SC belonged to genotype C, which clustered in the same large clade consisting of a population of Chinese genotype C strains but was found to be different from the other strains upon further differentiation. Compared to other Chinese genotype C strains, the BPIV-3 SC showed 70 unique nucleotide mutations and 13 unique amino acid mutations in the HN, P, and L proteins, suggesting a unique genetic evolution of BPIV-3 SC. In conclusion, we isolated and characterized a differential Chinese genotype C BPIV-3, which contributed to an understanding of the prevalence and evolution of BPIV-3 in China.

Secretome Analysis of High- and Low-Virulent Bovine Pasteurella multocida Cultured in Different Media.

Bovine Pasteurella multocida (P. multocida) serotype A is one of the major causes of bovine respiratory disease (BRD). We used data-independent acquisition (DIA) LC-MS/MS combined with bioinformatics analysis to identify proteins secreted by P. multocida. A total of 154 proteins were obtained from the supernatants of two isolates of bovine P. multocida serotype A (high virulent PmCQ2 and low virulent PmCQ6) cultured in Martin or BHI media, of which 50 were identified as putative secreted proteins. Further studies showed that Tuf, an elongation factor Tu, was highly expressed in P. multocida and secreted into infected tissues. Tuf stimulated strong innate immune responses of macrophages and had protective efficacy against P. multocida infection in a mouse model. The results provide insight into the secreted proteins of P. multocida and suggest new targets for vaccine development against P. multocida.

Transition from secukinumab to adalimumab in COVID-19-induced psoriasis flare-up treatment: A case report.

Coronavirus disease 2019 (COVID-19) is known to trigger systemic inflammation and elicit immune responses, which may disrupt the delicate balance of cytokines involved in psoriatic regulation. Compared to other therapies in dermatology, biologics used for immune-mediated dermatological diseases have been more extensively studied during the COVID-19 pandemic. Herein, we report a case of flare-up of previously well-controlled psoriasis shortly after infection with COVID-19, with treatment transition from secukinumab to adalimumab.

Penicillamine-induced degenerative dermopathy in a patient with Wilson's disease.

Penicillamine is a chelator that has been used in Wilson's disease, cystinuria, rheumatoid arthritis and heavy metal intoxication. We report a case of a 31-year-old man presented with skin atrophy, purpura and milia on the hips and shoulders after taking penicillamine for 1.5 years. According to literature review, this type of penicillamine-associated cutaneous adverse effect belongs to degenerative dermopathy, which mostly occurs on bony prominences and points of pressure in patients with Wilson's disease or cystinuria. Withdrawal or reduction of drug dose can improve the features of degenerative dermopathy.

Centrifugal lipodystrophy on a spectrum with lupus erythematosus panniculitis in children and efficacy and safety of hydroxychloroquine: A clinicopathological study.

This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n = 24) and CLD/LEP overlap (n = 5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female = 1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n = 2), subcutaneous nodules (n = 2) and alopecia along Blaschko's lines (n = 1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p = 0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p > 0.99). HCQ (5 mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5 mg/kg/d) was effective and safe for treating CLD (age >1.5 years), and early treatment and a regular long-term follow-up are essential.

Slc6a13 Deficiency Attenuates Pasteurella multocida Infection-Induced Inflammation via Glycine-Inflammasome Signaling.

We have previously demonstrated that Slc6a13-deficient (Slc6a13-/-; KO) mice are resistant to P. multocida infection, which might be in connection with macrophage-mediated inflammation; however, the specific metabolic mechanism is still enigmatic. Here we reproduce the less sensitive to P. multocida infection in overall survival assays as well as reduced bacterial loads, tissue lesions, and inflammation of lungs in KO mice. The transcriptome sequencing analysis of wild-type (WT) and KO mice shows a large number of differentially expressed genes that are enriched in amino acid metabolism by functional analysis. Of note, glycine levels are substantially increased in the lungs of KO mice with or without P. multocida infection in comparison to the WT controls. Interestingly, exogenous glycine supplementation alleviates P. multocida infection-induced inflammation. Mechanistically, glycine reduces the production of inflammatory cytokines in macrophages by blocking the activation of inflammasome (NALP1, NLRP3, NLRC4, AIM2, and Caspase-1). Together, Slc6a13 deficiency attenuates P. multocida infection through lessening the excessive inflammatory responses of macrophages involving glycine-inflammasome signaling.

Chlorogenic acid and caffeine combination attenuates adipogenesis by regulating fat metabolism and inhibiting adipocyte differentiation in 3T3-L1 cells.

Obesity is a complex disease spreading in the world. In our previous studies, chlorogenic acid (CGA) and caffeine had ever been reported to reduce the body weight gain and fat accumulation in mice. This study investigated the anti-obesity effect of CGA and caffeine on 3T3-L1 cells. According to triglyceride (TG) assay and Oil-Red O staining, 40 µg/ml CGA and 160 µg/ml caffeine reduced TG content. Moreover, CGA + caffeine inhibited the mRNA expression of major adipogenic markers, PPAR-γ2, and C/EBPα in the metaphase and anaphase stages of differentiation induction (Day 2 and 4). CGA + caffeine improved P-AMPK/AMPK accompanied by decreasing the expression of GPDH and FAS to depress the lipid synthesis, increasing the mRNA expression of ACO and CAT to promote fatty acid oxidation and up-regulated the expression of hydrolysis-related enzyme adipose TG lipase (ATGL) and P-HSL/HSL. Furthermore, CGA + caffeine improved the expression of Glut4 which promoted the glucose transport. Taken together, these data demonstrated CGA + caffeine inhibited 3T3-L1 cells differentiation in the middle and late stages and reduced the fat accumulation through AMPK pathway by regulating the fat metabolism-related enzyme in 3T3-L1 cells to attenuates adipogenesis. PRACTICAL APPLICATIONS: The aim of this study was to elucidate the potential role of chlorogenic acid and caffeine in the treatment of obesity.

Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient.

We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.

RNA-binding motif protein 43 (RBM43) suppresses hepatocellular carcinoma progression through modulation of cyclin B1 expression.

RNA-binding proteins play key roles in the posttranscriptional regulation of mRNA during cancer progression. Here, we show that RNA-binding motif protein 43 (RBM43) is significantly downregulated in human tumors, and its low expression is correlated with poor prognosis in patients with HCC. Overexpression of RBM43 suppressed cell proliferation in culture and resulted in the growth arrest of tumor xenografts, whereas downregulating RBM43 played an opposite role. We have also demonstrated that overexpression or knockdown of RBM43 affects the cell-cycle progression of liver cancer cells. Mechanistically, RBM43 directly associated with the 3'UTR of Cyclin B1 mRNA and regulated its expression. Moreover, loss of Rbm43 in mice promoted liver carcinogenesis and HCC development after diethylnitrosamine (DEN)-carbon tetrachloride (CCl4) treatment. Taken together, our data indicate that RBM43 is a tumor suppressor that controls the cell cycle through modulation of Cyclin B1 expression, providing evidence that RBM43 is particularly important in HCC.

Pharmacokinetics of extended-release ivermectin microspheres after oral administration to healthy pigs.

We compared the pharmacokinetics of ivermectin premix and ivermectin microspheres in pigs after single and multiple administration regimes. In the single-dose experiments, 24 piglets were randomly divided into three groups and given ivermectin at 0.3 mg/kg using (a) 1.0% ivermectin administered subcutaneously, (b) 0.25% ivermectin premix orally, and (c) 0.25% ivermectin microspheres orally. In the multiple-dose experiment, 6 pigs in two equal groups received ivermectin premix and microspheres orally at 0.3 mg/kg for 7 consecutive days to monitor the valley plasma levels. The plasma samples were detected by fluorescence high-performance liquid chromatography, and concentration-time data were fitted to a noncompartmental model. After oral administration of ivermectin microspheres at a single dose, the elimination rate constant (Kel), the half-life (t1/2 ), the peak time (Tmax ), the mean residence time (MRT), and the peak concentration (Cmax ) were 0.012 ± 0.0031/hr, 59.94 ± 20.18 hr, 9.50 ± 0.93 hr, 55.96 ± 11.40 hr, and 37.75 ± 3.45 ng/ml, respectively. The Cmax of microspheres was not statistically different (p > .05) compared with that of premix groups (39.81 ± 5.83 ng/ml). Moreover, the AUC of the microcapsule groups was increased from 1,129.76 ± 245.62 to 1,607.33 ± 343.35 hr ng/ml compared with the premix groups, and the relative bioavailability increased by an average of 17.53% after oral administration with ivermectin microspheres. Multiple-dose administration also indicated pigs fed with ivermectin microspheres can get a higher minimum steady-state concentration and a longer maintenance time than ivermectin premix.

Changes and determinants of health-related quality of life among people newly diagnosed with HIV in China: a 1-year follow-up study.

PURPOSE: This study aimed to investigate changes in health-related quality of life (HRQoL) among people newly diagnosed with HIV and to identify factors associated with HRQoL. METHODS: Newly diagnosed HIV-positive individuals were consecutively recruited and assessed at baseline and 1-year follow-up after diagnosis. HRQoL was measured through the physical health summary score (PHS) and mental health summary score (MHS) derived from the Medical Outcomes Study HIV Health Survey. Socio-demographic, clinical, and psychological information was also collected at both times. Generalized estimating equations were applied to explore factors associated with HRQoL in 1 year. RESULTS: A total of 410 participants were included. After 1 year, significant increases were observed for both the mean PHS score (53.5-55.0; p = 0.009) and the mean MHS score (44.2-49.0; p < 0.001). Older age (p = 0.024), rural household registration (p = 0.031), HIV-related symptoms (p < 0.001), and depression (p = 0.014) were negatively associated with PHS. Additionally, the negative association between stress and PHS increased over time (ß = - 0.07 for the baseline; ß = - 0.18 for the 12-month follow-up; p < 0.001). HIV-related symptoms, depression, lower social support, and higher levels of stress (all p < 0.001) were negatively associated with MHS. Additionally, the negative relationship between stress and MHS was stronger among participants who were asymptomatic (p = 0.015). CONCLUSION: A relatively lower HRQoL among HIV-infected people shortly after HIV diagnosis and an increase in HRQoL among people 1 year after HIV diagnosis were observed. Additional attention should be paid to individuals of older age, from rural areas, with HIV-related symptoms, with depression, with high levels of stress, and with a lack of social support.

Efficient Photoelectrochemical Water Splitting by g-C3N4/TiO2 Nanotube Array Heterostructures.

Well-ordered TiO2 nanotube arrays (TNTAs) decorated with graphitic carbon nitride (g-C3N4) were fabricated by anodic oxidization and calcination process. First, TNTAs were prepared via the anodic oxidation of Ti foil in glycerol solution containing fluorinion and 20% deionized water. Subsequently, g-C3N4 film was hydrothermally grown on TNTAs via the hydrogen-bonded cyanuric acid melamine supramolecular complex. The results showed that g-C3N4 was successfully decorated on the TNTAs and the g-C3N4/TNTAs served as an efficient and stable photoanode for photoelectrochemical water splitting. The facile deposition method enables the fabrication of efficient and low-cost photoanodes for renewable energy applications.

PARP12 (ARTD12) suppresses hepatocellular carcinoma metastasis through interacting with FHL2 and regulating its stability.

PARP12 is a mono-ADP-ribosyltransferase, but its function remains largely unknown. Here, we identified four-and-a-half LIM-only protein 2 (FHL2) as a functional partner of PARP12 through protein affinity purification. Although PARP12 did not mono-ADP-ribosylate FHL2 in vitro and in vivo, PARP12 deficiency decreased the protein level of FHL2 by promoting its ubiquitination and increased the expression level of transforming growth factor beta1 (TGF-ß1), which is independent of PARP12 enzymatic activity. We also provided evidence that PARP12 deficiency increased the migration and invasion of hepatocellular carcinoma (HCC) cells and promoted HCC metastasis in vivo by regulating the epithelial-mesenchymal transition process. These results indicated that PARP12 is a tumor suppressor that plays an important role in HCC metastasis through the regulation of FHL2 stability and TGF-ß1 expression.

Noble-metal-free tungsten oxide/carbon (WOx/C) hybrid manowires for highly efficient hydrogen evolution.

Developing active, stable, and low-cost electrocatalysts to generate hydrogen is a great challenge in the fields of chemistry and energy. Nonprecious metal catalysts comprised of inexpensive and earth-abundant transition metals are regarded as a promising substitute for noble metal catalysts used in hydrogen evolution reaction (HER), but are still practically unfeasible mainly due to unsatisfactory activity and durability. Here we report a facile two-step preparation method for WOx nanowires with high concentration of oxygen vacancies (OVs) via calcination of W-polydopamine compound precursors. The resulting hybrid material possesses a uniform and ultralong 1D nanowires structure and a rough and raised surface, which can effectively improve the specific surface area. The products exhibit excellent performance for H2 generation: the required overpotentials for 1 and 10 mA cm-2 are 18 and 108 mV, the Tafel slope is 46 mV/decade, and the electrochemically active surface area is estimated to be ∼77.0 m2 g-1. After 1000 cycles, the catalyst works well without significant current density drop. Our experimental results verified metallic transition metal oxides as superior non-Pt electrocatalysts for practical hydrogen evolution reactions.

[Characteristics of health seeking behaviors for patients with psoriasis in a general hospital].

OBJECTIVE: To explore the characteristics of health seeking behaviors and relevant factors among the outpatients with psoriasis in a general hospital, and to provide scientific evidence to modify the inappropriate health seeking behaviors for psoriasis patients and improve the therapeutic effect. 
 METHODS: Using cross-sectional study design, a dermatological clinic in a general hospital was selected for this study. Two hundred psoriasis outpatients from 1st April to 30th September in 2014 were enrolled. A series of questionnaires were used to collect information regarding the social-demographic characteristics, health seeking behaviors, knowledge on psoriasis, and depressive and anxious symptoms.
 RESULTS: Among 200 psoriasis outpatients, 141 patients (70.5%) experienced transfer treatment. One hundred and eighty-two patients (91.0%) went to formal hospitals in county for treatment when symptoms were firstly displayed; the other 18 patients (9.0%) went to village or community clinics, or the private clinics. Over 50% patients chose municipal hospital and 35.0% patients went to provincial hospital for medical treatment among the 182 patients. Ninety-one percent of the patients made decision for the first treatment after consulting with their spouses or relatives. According to the definition of the appropriate health seeking behavior in this study, 50 patients (25%) had inappropriate health seeking behaviors. Logistic regression analysis showed inappropriate health seeking behaviors correlated with the family whose income was less than 3 000 yuan per person per month (OR=2.232, 95%CI 1.086 to 4.585), patients who made the decision for the treatment with no discussion with other people when the symptoms appeared (OR=3.016, 95%CI 1.023 to 8.893), and the high score of the International Psoriasis Severity Index (OR=1.043, 95%CI 1.001 to 1.088). 
 CONCLUSION: The dermatological practitioner should pay more attention to the factors, such as social-demographical characteristics, especially the low level of family income and their treatment experience. It is necessary for the general hospital to conduct health education for psoriasis outpatients to promote their appropriate health seeking behaviors.

Cross-Culture Validation of the HIV/AIDS Stress Scale: The Development of a Revised Chinese Version.

BACKGROUND: Being HIV-infected is a stressful experience for many individuals. To assess HIV-related stress in the Chinese context, a measure with satisfied psychometric properties is yet underdeveloped. This study aimed to examine the psychometric characteristics of a simplified Chinese version of the HIV/AIDS Stress Scale (SS-HIV) among people living with HIV/AIDS in central China. METHOD: A total of 667 people living with HIV (92% were male) were recruited from March 1st 2014 to August 31th 2015 by consecutive sampling. A standard questionnaire package containing the Chinese HIV/AIDS Stress Scale (CSS-HIV), the Chinese Patient Health Questionnaire-9 (PHQ-9), and the Chinese Generalized Anxiety Disorder Scale (GAD-7) were administered to all participants, and 38 of the participants were selected randomly to be re-tested in four weeks after the initial testing. RESULTS: Our data supported that a revised 17-item CSS-HIV had adequate psychometric properties. It consisted of 3 factors: emotional stress (6 items), social stress (6 items) and instrumental stress (5 items). The overall Cronbach's α was 0.906, and the test-retest reliability coefficient was 0.832. The revised CSS-HIV was significantly correlated with the number of HIV-related symptoms, as well as scores on the PHQ-9 and GAD-7, indicating acceptable concurrent validity. CONCLUSION: The 17-item Chinese version of the SS-HIV has potential research and clinical utility in identifying important stressors among the Chinese HIV-infected population and in understanding the effects of stress on adjustment to HIV.

[Emotional problems and related factors in patients with HIV/AIDS].

OBJECTIVE: To investigate the prevalence and related factors of emotional problems of newly identified patients with HIV/AIDS in Changsha, Hunan Province, and to provide scientific evidence for the mental health intervention in this special population. METHODS: A total of 370 patients with HIV/AIDS who were newly identified by the Center for Disease Prevention and Control in Changsha City from March 1, 2013 to February 28, 2014 were investigated. Self-designed questionnaire, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), HIV/AIDS Stress Scale and Social Support Rating Scale (SSRS) were performed to assess the prevalence of depression, the anxiety symptoms, the HIV related stress and the status of social support. RESULTS: The prevalence of depression and anxiety were 40.3% (PHQ-9 ≥ 10 points) and 30.5% (GAD-7 ≥ 10 points), respectively. Severe depressive symptoms (PHQ-9≥20 points) and severe anxiety (GAD-7 ≥ 15 points) accounted for 8.1% and 14.3%, respectively. Hierarchical regression analysis showed that the status of employment (b=-3.407, P<0.001; b=-2.799, P=0.001), the sexual orientation (b=1.903, P=0.008; b=1.314, P=0.034), the resident status (b=-1.995, P=0.012; b=-2.167, P=0.002), the emergence of HIV-related symptoms(b=4.578, P<0.001; b=3.652, P<0.001) and the HIV related stress (b=0.081, P<0.001; b=0.090, P<0.001) were the predictors for both depressive and anxious emotional problems whereas the social support (b=-0.046, P=0.044) was the predictor for depressive emotional problems. Both anxiety (ΔR2=54.7%, P<0.001) and depression (ΔR2=55.8%, P<0.001) were strong predictors for patients with HIV/AIDS. CONCLUSION: Depression and anxiety are prevalent among the newly identified patients with HIV/ AIDS. Psychosocial support and basic mental health services should be integrated into the current HIV/AIDS care system.

Chlorogenic acid and caffeine in combination inhibit fat accumulation by regulating hepatic lipid metabolism-related enzymes in mice.

Obesity has become a public health concern due to its positive association with the incidence of many diseases, and coffee components including chlorogenic acid (CGA) and caffeine have been demonstrated to play roles in the suppression of fat accumulation. To investigate the mechanism by which CGA and caffeine regulate lipid metabolism, in the present study, forty mice were randomly assigned to four groups and fed diets containing no CGA or caffeine, CGA, caffeine, or CGA+caffeine for 24 weeks. Body weight, intraperitoneal adipose tissue (IPAT) weight, and serum biochemical parameters were measured, and the activities and mRNA and protein expression of lipid metabolism-related enzymes were analysed. There was a decrease in the body weight and IPAT weight of mice fed the CGA+caffeine diet. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, TAG and leptin of mice fed the CGA+caffeine diet. The activities of carnitine acyltransferase (CAT) and acyl-CoA oxidase (ACO) were increased in mice fed the caffeine and CGA+caffeine diets, while the activity of fatty acid synthase (FAS) was suppressed in those fed the CGA+caffeine diet. The mRNA expression levels of AMP-activated protein kinase (AMPK), CAT and ACO were considerably up-regulated in mice fed the CGA+caffeine diet, while those of PPARγ2 were down-regulated. The protein expression levels of AMPK were increased and those of FAS were decreased in mice fed the CGA+caffeine diet. These results indicate that CGA+caffeine suppresses fat accumulation and body weight gain by regulating the activities and mRNA and protein expression levels of hepatic lipid metabolism-related enzymes and that these effects are stronger than those exerted by CGA and caffeine individually.