Therapeutic Effect of Lecigel, Cetiol®CC, Activonol-6, Activonol-M, 1,3-Propanediol, Soline, and Fucocert® (LCAA-PSF) Treatment on Imiquimod-Induced Psoriasis-like Skin in Mice.

The individual ingredients of 1,3-Propanediol, Soline, and Fucocert® (PSF) are often used as cosmetic formulations in skin care. In addition, the mixture of Lecigel, Cetiol®CC, Activonol-6, and Activonol-M (LCAA) is often used as a cosmetic base. However, whether the combination of LCAA with PSF (LCAA-PSF) exerts a therapeutic effect on psoriasis remains unclear. In this study, mice induced with imiquimod (IMQ) were divided into three groups and administered 100 mg/day of LCAA, 100 mg/day of LCAA-PSF, or Vaseline on the dorsal skin of each mouse. Weight-matched mice treated with Vaseline alone were used as controls. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay(ELISA) were used to assess tissue morphology and inflammatory cytokines. RNA sequencing analysis was used to predict the mechanism underlying the action of LCAA-PSF against psoriasis, while immunohistochemical analysis validation was used to identify pertinent molecular pathways. The results demonstrated that LCAA-PSF alleviated IMQ-induced keratinocyte differentiation/ proliferation bydecreasingthe serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17A and the epidermisof TGFß, Ki67, CK5/6, and VEGF expression, which is associated with angiogenesis and keratinocyte differentiation/ proliferation. These findings highlight the antipsoriatic activity of LCAA-PSF in a psoriasis-like mouse model and suggest this may occurvia the inhibition of inflammatory factor secretionand the TGFß-related signal pathway.

Preparation and Evaluation of Nanoemulsion Formulation Containing Kojic Acid and Kojyl 3-aminopropylphosphonic Acid.

BACKGROUND: The kojyl 3-aminopropylphosphonic acid (KAP) was synthesized by kojic acid (KA) with a 3-aminopropylphosphonic acid. Which is more stable than KA and showed better skin penetration and anti-pigmentation efficacy in melanocytes. However, up till now, there have been no studies aimed at incorporating KAP into an emulsion system and evaluating its effectiveness. OBJECTIVE: We develop a novel skin-lightening agent using KAP as the active ingredient and a low-cytotoxic nanoemulsion as the delivery system in this study. METHOD: The sorbitan monooleate and polysorbate surfactants with polyethylene glycol (PEG) co-surfactant were used to generate a nanoemulsion system. RESULT: The transparency and particle size stability over various storage times indicate that the formulated nanoemulsions are suitable for long-term storage. Besides, results demonstrate that the anti-pigmentation function of KA and KAP-containing nanoemulsions (NE-KA and NEKAP) evidently outperformed that of the non-packed KA and KAP group. Despite having the lowest concentration among other treatments, NE-KAP was able to reduce melanin content to approximately 80% of the blank. CONCLUSION: Our findings suggest that this newly developed nanoemulsion containing KAP could potentially serve as a sustainable alternative to hydroquinone for treating dermal hyperpigmentation disorders in future applications.

Effects of acute slackline exercise on executive function in college students.

Background: Physical exercise as an intervention for improving cognitive function, especially executive function, is receiving increasing attention because it is easily accessible, cost-effective and promises many additional health-related benefits. While previous studies focused on aerobic exercise and resistance exercise, recent findings have suggested that exercise with high coordination demand elicits beneficial effects on executive function. We therefore examined the effects of an acute slackline exercise on the executive functions of young adults. Methods: In a crossover experimental design, 47 healthy participants (21 females), ranging in age from 18 to 27 years (M = 19.17, SD = 1.94) were randomly assigned to different sequences of two conditions (slackline exercise and film-watching). Before and after the 50 min intervention, a modified Simon task was used to assess participants' executive function (inhibitory control and cognitive flexibility). Results: College students showed better inhibitory control performance as indicated by shorter reaction times following acute slackline exercise than those who participated in the film-watching session. As there was no difference in accuracy between the slackline exercise and film-watching sessions, the shortened reaction time after slackline exercise provides evidence against a simple speed-accuracy trade-off. Conclusion: Compared with film-watching, acute slackline exercise provides favorable effects on executive function necessitating inhibition in young adults. These findings provide insight into exercise prescription and cognition, and further evidence for the beneficial effects of coordination exercise on executive functions.

Small-molecule PIK-93 modulates the tumor microenvironment to improve immune checkpoint blockade response.

Immune checkpoint inhibitors (ICIs) targeting PD-L1 immunotherapy are state-of-the-art treatments for advanced non-small cell lung cancer (NSCLC). However, the treatment response of certain patients with NSCLC is unsatisfactory because of an unfavorable tumor microenvironment (TME) and poor permeability of antibody-based ICIs. In this study, we aimed to discover small-molecule drugs that can modulate the TME to enhance ICI treatment efficacy in NSCLC in vitro and in vivo. We identified a PD-L1 protein-modulating small molecule, PIK-93, using a cell-based global protein stability (GPS) screening system. PIK-93 mediated PD-L1 ubiquitination by enhancing the PD-L1-Cullin-4A interaction. PIK-93 reduced PD-L1 levels on M1 macrophages and enhanced M1 antitumor cytotoxicity. Combined PIK-93 and anti-PD-L1 antibody treatment enhanced T cell activation, inhibited tumor growth, and increased tumor-infiltrating lymphocyte (TIL) recruitment in syngeneic and human peripheral blood mononuclear cell (PBMC) line-derived xenograft mouse models. PIK-93 facilitates a treatment-favorable TME when combined with anti-PD-L1 antibodies, thereby enhancing PD-1/PD-L1 blockade cancer immunotherapy.

The unique contribution of motor ability to visuospatial working memory in school-age children: Evidence from event-related potentials.

This study investigated the unique contribution of motor ability to visuospatial working memory (VSWM) and neuroelectric activity in school-age children. Seventy-six children aged 8.7 ± 1.1 years participated in this cross-sectional study. We assessed aerobic fitness using the 20-m endurance shuttle run test, muscular fitness (endurance, power) using a standard test battery, and motor ability (manual dexterity, ball skills, and static and dynamic balance) using the Movement Assessment Battery for Children. A modified delayed match-to-sample test was used to assess VSWM and the P3 component of event-related potentials. Hierarchical regression analyses indicated that greater aerobic fitness was associated with smaller coefficient of variation of reaction time (p = .008), greater muscular fitness was associated with higher response accuracy (p = .022), greater motor ability was associated with higher response accuracy (p < .001) and increased P3 mean amplitude (p < .001) after controlling for age. Furthermore, the positive associations of motor ability with response accuracy (p = .001) were independent of muscular fitness. The findings from this study provide new insight into the differential associations between health-related fitness domains and VSWM, highlighting the influence of motor ability on brain health and cognitive development during childhood.

WAKE-mediated modulation of cVA perception via a hierarchical neuro-endocrine axis in Drosophila male-male courtship behaviour.

The nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as wake) modulates membrane levels of GABAA receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour.

Improved Fixation Stability of a Dedicated Rib Fixation System in Flail Chest: A Retrospective Study.

Background and Objectives: Flail chest typically results from major trauma to the thoracic cage and is accompanied by multiple rib fractures. It has been well documented that surgical fixation of rib fractures can decrease both morbidity and mortality rates. This study aimed to evaluate the effectiveness of a dedicated APS Rib Fixation System, which features a pre-contoured design based on anatomical rib data of the Asian population. Materials and Methods: We reviewed 43 consecutive patients, who underwent surgical stabilization for flail chest with the traditional Mini bone plate (n = 20), APS plate (n = 13), or Mini + APS (n = 10). Demographic and injury variables were documented. We used X-ray radiography to determine plate fractures and screw dislocations after surgical fixation. Results: No statistical differences were noted in the demographic or injury variables. APS plates demonstrated fewer cases of plate fractures and screw dislocations than Mini plates (OR = 0.091, p = 0.008). Conclusions: The pre-contoured design of the APS plate demonstrated a superior rib implant failure rate as compared to the traditional Mini bone plate. Our study indicates that the APS plate may serve as an effective surgical tool for the treatment of flail chest.

Reply to the letter to the editor: Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: An open-label, parallel-group study.

This is a response to the comment on our published article "Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: An open-label, parallel-group study". Safer et al., questioned about the procedure and consistency of bioelectrical impedance analysis (BIA) measurement at the baseline and follow up visits. Also, they wondered whether the BIA device we used is validated in Taiwanese older adults with sarcopenia. We followed the standard protocols and the procedures were consistent at each measurement. Magnetic resonance image (MRI) and dual energy X ray absorptiometry (DXA) are gold standards for quantifying muscle mass. According to the clinical trials performed in Taiwan, the BIA device we used showed a significant correlation with MRI and DXA and is validated in older adults with sarcopenia in Taiwan. Trial registration: ClinicalTrials.gov NCT03860194.

Genome-Wide Association Study of Lithium-Induced Dry Mouth in Bipolar I Disorder.

Dry mouth is a rather common unpleasant adverse drug reaction (ADR) to lithium treatment in bipolar disorders that often lead to poor adherence or early dropout. The aim of this study was to identify the genetic variants of dry mouth associated with lithium treatment in patients with bipolar I (BPI) disorder. In total, 1242 BPI patients who had ever received lithium treatment were identified by the Taiwan Bipolar Consortium for this study. The proportions of patients who experienced impaired drug compliance during lithium medication were comparable between those only with dry mouth and those with any other ADR (86% and 93%, respectively). Dry mouth appeared to be the most prevalent (47.3%) ADR induced by lithium treatment. From the study patients, 921 were included in a genome-wide association study (GWAS), and replication was conducted in the remaining 321 patients. The SNP rs10135918, located in the immunoglobulin heavy chain locus (IGH), showed the strongest associations in the GWAS (p = 2.12 × 10-37) and replication groups (p = 6.36 × 10-13) (dominant model) for dry mouth with a sensitivity of 84.9% in predicting dry mouth induced by lithium. Our results may be translated into clinical recommendation to help identify at-risk individuals for early identification and management of dry mouth, which will improve medication adherence.

Using a Cellular System to Directly Assess the Effects of Cosmetic Microemulsion Encapsulated DeoxyArbutin.

DeoxyArbutin (dA) is a tyrosinase inhibitor that has effective skin-lightening activity and has no obvious cytotoxicity toward melanocytes. With the aim of directly evaluating the effects of microemulsions containing dA on cells, we developed oil-in-water (O/W) microemulsions with relatively lower cytotoxicities by using polysorbate-series surfactants. Measurement of the transparent properties and particle size analysis at different storage time periods revealed that the developed microemulsions were stable. Moreover, the developed microemulsions had direct effects on B16-F10 mouse melanoma cells. The anti-melanogenesis activities of dA-containing microemulsions were evidently better than that of the free dA group. The results demonstrated that the developed microemulsion encapsulating dA may allow the use of deoxyArbutin instead of hydroquinone to treat dermal hyperpigmentation disorders in the future.

A Taiwanese study on real-world evidence with vortioxetine in patients with major depression in Asia (TREVIDA).

OBJECTIVE: The TREVIDA study aimed to evaluate vortioxetine for the treatment of major depressive disorder (MDD) in Taiwanese adults. METHODS: Patients with active depressive episode were recruited in this non-interventional, prospective, multi-site study conducted between June 2019 and August 2020 in Taiwan. Patient eligibility was independent of the physician's decision to prescribe vortioxetine for an MDD episode. Vortioxetine was initiated on the first visit. Depression severity, cognitive function, work productivity, functioning and safety were evaluated over 3 months. RESULTS: Overall, 242 patients were analyzed. At baseline, 70.7% and 90.4% of patients had moderately severe-to-severe depression based on PHQ-9 (Patient Health Questionnaire-9) and TDQ (Taiwanese Depression Questionnaire), respectively. By Month 3, significant improvements from baseline in depression severity (mean [SD] changes in PHQ-9, TDQ and CGI-S [Clinical Global Impression-Severity]: -6.3 [7.3]; -13.2 [14.0]; -1.5 [1.3], respectively), cognitive function (mean [SD] change in PDQ-D: -8.0 [17.5]), functioning (mean [SD] change in SDS: -5.4 [7.6]), and presenteeism (38.9% from 56.3%), work productivity loss (40.9% from 58.7%) and activity impairment (43.2% from 61.0%) were observed (p < .001 for all). By month 3, patient-reported (PHQ-9) response and remission rates were 43.4% and 52.9%, respectively; physician-reported (CGI-S) response and remission rates were 29.0% and 31.6%, respectively. Vortioxetine was well-tolerated and no unexpected side effects were reported. CONCLUSIONS: Vortioxetine reduced depression severity and improved cognitive function, work productivity, and functioning in Taiwanese patients with MDD in the real-world setting. Vortioxetine was well-tolerated in this Taiwanese population.

Up-regulation of proactive control is associated with beneficial effects of a childhood gymnastics program on response preparation and working memory.

The current study focused on the effects of an 8-week motor skill-based physical activity (i.e., gymnastics) program on the contingent negative variation derived from event-related brain potentials (CNV-ERP) during a working memory task in children. Children aged 7-10 years old were assigned to a gymnastics group (n = 26) or a wait-list control group (n = 24). The gymnastics group engaged in a gymnastics program whereas children in the control group were asked to maintain their typical routine during the intervention period. Working memory performance was measured by a delayed-matching working memory task, accompanied by CNV-ERP collection. The results revealed significant improvement of response accuracy from pre-test to post-test in the gymnastic group regardless of memory demands. Moreover, significant increase from pre-test to post-test in the initial CNV was observed in the gymnastic group regardless of memory demands. Bivariate correlations further indicated that, in the gymnastic group, increases in response accuracy from pre-test to post-test were correlated with increases in initial CNV from pre-test to post-test in task conditions with lower and higher memory loads. Overall, the current findings suggest that up-regulation of proactive control may characterize the beneficial effects of childhood motor skill-based physical activity on working memory.

Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: An open-label, parallel-group study.

BACKGROUND & AIMS: Sarcopenia is defined as a syndrome characterized by declines in skeletal muscle mass and strength or an alteration in physical function. Although some studies showed nutritional supplementation alone might have health benefits for older sarcopenic patients, their results were inconsistent and remain controversial. The objective of this study was to evaluate if a diet with high protein supplementation (Supp) can lead to better improvement than additional protein intake via dietary counseling (Diet) in maintaining the muscle mass and strength among sarcopenic elders. METHODS: This was an open-label, parallel-group (Supp vs. Diet) trial. In total, 56 sarcopenic elders completed this study. All subjects were advised to achieve adequate protein intake (1.2-1.5 g/kg body weight/day). This amount of protein is recommended for the elderly and is thought to prevent or retard muscle loss due to aging. The diet group (n = 28) was recommended to consume an ordinary protein-rich diet via counselling whereas the Supp group (n = 28) received a vitamin D- and leucine-enriched whey protein supplement for 12 weeks. The appendicular muscle mass index (AMMI), handgrip strength, gait speed, and calorie and macronutrients intake were evaluated after 4 and 12 weeks of the diet intervention. RESULTS: Total energy and protein intake increased in both groups. The Supp group had higher intake than the Diet group. The AMMI increased in both groups, and handgrip strength improved in the Diet group. However, no significant differences in AMMI or handgrip strength were found between the two groups. Compared to the Diet group, the Supp group had better improvement in gait speed after 12 weeks of the supplement intervention especially in subjects younger than 75 years. CONCLUSIONS: The AMMI can be improved as long as sufficient protein is consumed (1.2-1.5 g/kg body weight/day) in sarcopenic elders. Nutritional supplement allows the sarcopenic elderly to more conveniently meet their protein requirements. Supplementation with whey protein and vitamin D can further improve gait speed in elderly sarcopenic subjects, especially in the "younger" age group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03860194.

Human Microfibrillar-Associated Protein 4 (MFAP4) Gene Promoter: A TATA-Less Promoter That Is Regulated by Retinol and Coenzyme Q10 in Human Fibroblast Cells.

Elastic fibers are one of the major structural components of the extracellular matrix (ECM) in human connective tissues. Among these fibers, microfibrillar-associated protein 4 (MFAP4) is one of the most important microfibril-associated glycoproteins. MFAP4 has been found to bind with elastin microfibrils and interact directly with fibrillin-1, and then aid in elastic fiber formation. However, the regulations of the human MFAP4 gene are not so clear. Therefore, in this study, we firstly aimed to analyze and identify the promoter region of the human MFAP4 gene. The results indicate that the human MFAP4 promoter is a TATA-less promoter with tissue- and species-specific properties. Moreover, the promoter can be up-regulated by retinol and coenzyme Q10 (coQ10) in Detroit 551 cells.

Protective effects and network analysis of natural compounds obtained from Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae against RANKL-induced osteoclastogenesis in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis is one of the most common bone diseases; it is characterized by bone loss and is a risk factor for hip fracture. Chinese herbal medicines (CHMs) and their related natural compounds have been used for treating many diseases, including bone diseases, since ancient times in China and are regarded as a cost-effective complementary therapy. AIM OF THE STUDY: The goal of this study was to investigate the osteoprotective mechanisms of these three Chinese herbs and their related natural compounds. The effects of CHMs and related natural compounds on RANKL-induced osteoclastogenesis in vitro were investigated. MATERIALS AND METHODS: A network pharmacology method was applied to study CHM-related natural compounds and their osteoporosis targets. In addition, their effect on RANKL-induced osteoclastogenesis in RAW264.7 cells was also investigated in vitro. RESULTS: Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae exhibited protective effects against mortality in hip fracture patients. Furthermore, these three herbs inhibited RANKL-induced TRAP activities and reduced the expression of bone resorption-related genes in RAW264.7 cells. Network analysis of natural compound (ingredient)-target interactions identified 11 natural compounds. Signal pathway analyses suggested that these compounds may target cytokine-cytokine receptor interactions, including RANKL-induced osteoclastogenesis. Five novel natural compounds exhibited reduced RANKL-induced TRAP activities and bone resorption-related gene expression. CONCLUSION: The clinically used CHMs, Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae, and natural compounds obtained from them may suppress RANKL-induced osteoclastogenesis in vitro.

Preparation and Evaluation of Novel Transfersomes Combined with the Natural Antioxidant Resveratrol.

Resveratrol (tran-3,5,4'-trihydroxystibene, RSV) is a kind of polyphenol which has anti-inflammatory, antioxidant, anti-allergy, and anti-cancer properties, as well as being a scavenger of free radicals and preventing cardiovascular diseases. However, it is quite unstable in light, heat, and other conditions, and decays easily due to environmental factors. For these reasons, this study used a new type of carrier, transfersome, to encapsulate RSV. Transfersome consists of phosphatidyl choline (PC) from a liposomal system and non-ionic edge activators (EA). EA are an important ingredient in the formulation of transfersome; they can enhance the flexibility of the lipid bimolecular membrane of transfersome. Due to its ultradeformability, it also allows drugs to penetrate the skin, even through the stratum corneum. We hope that this new encapsulation technique will improve the stability and enhance the permeability of RSV. Concluding all the tested parameters, the best production condition was 5% PC/EA (3:1) and 5% ethanol in distilled water, with an ultrasonic bath and stirring at 500 rpm, followed by high pressure homogenization. The optimal particle size was 40.13 ± 0.51 nm and the entrapment efficiency (EE) was 59.93 ± 0.99%. The results of antioxidant activity analysis showed that transfersomes were comparable to the RSV group (unencapsulated). During in vitro transdermal delivery analysis, after 6 h, D1-20(W) increased 27.59% by accumulation. Cell viability assay showed that the cytotoxicity of D3-80(W) was reduced by 34.45% compared with the same concentration of RSV. Therefore, we successfully prepared RSV transfersomes and also improved the stability, solubility, and safety of RSV.

Effects of Chinese herbal medicine therapy on survival and hepatic outcomes in patients with hepatitis C virus infection in Taiwan.

BACKGROUND: Chinese herbal medicine (CHM) is a complementary natural medicine that is used widely for the treatment of hepatic diseases. The aim of this study was to investigate the effects of the long-term use of CHM for the treatment of liver diseases, as prescribed by TCM doctors, on overall mortality and hepatic outcomes in patients with HCV. PATIENTS AND METHODS: We identified 98788 patients with HCV. Of these, 829 and 829 patients who were users and non-users of CHM, respectively, were matched for age, gender, CCI, and comorbidities prior to CHM treatment. The chi-squared test, Cox proportional hazard model, Kaplan--Meier method, and log-rank test were used for comparisons. RESULTS: CHM users had a lower risk of overall mortality than non-users after adjustment for comorbidities by using a multivariate Cox proportional hazard model (p-value < 0.001; HR: 0.12, 95% CI: 0.06-0.26). In addition,the CHM users had a lower risk of liver cirrhosis than non-users after adjustment for comorbidities (p-value = 0.028; HR: 0.29, 95% CI: 0.09-0.88). The 12-year cumulative incidences of overall mortality and liver cirrhosis were lower in the CHM group (p-value < 0.05 for both, log rank test). The CHM co-prescription for Dan-Shen, Bie-Jia, Jia-Wei-Xiao-Yao-San => E-Shu was found to occur most often associated for the specific treatment of HCV infection. CONCLUSION: CHM as adjunctive therapy may reduce the overall mortality and the risk of liver cirrhosis in patients with HCV. The comprehensive list of the herbal medicines that may be used for the treatment of patients with HCV may be useful in future scientific investigations or for future therapeutic interventions to prevent negative hepatic outcomes in patients with HCV.

Zr-MOF/Polyaniline Composite Films with Exceptional Seebeck Coefficient for Thermoelectric Material Applications.

Controlling the polymerization of aniline in the presence of zirconium-based metal-organic frameworks (Zr-MOFs) using polystyrene sulfonic acid as a dopant resulted in the formation of a new type of free-standing thermoelectric composite film. Polyaniline chains interpenetrate into the Zr-MOFs to enhance the crystallinity of polyaniline, resulting in an improved degree of electrical conductivity. In addition, the inherent porosity of the Zr-MOFs functions to suppress the increase in thermal conductivity, thus dramatically promoting a negative Seebeck coefficient. When 20 wt % Zr-MOF was used, a power factor of up to 664 µW/(m K2) was obtained, which was accompanied by a surprisingly large, negative Seebeck coefficient. The new class of MOF-based composites offers a new direction for developing new types of efficient thermoelectric materials.

Evaluation of Oral Antiretroviral Drugs in Mice With Metabolic and Neurologic Complications.

Antiretroviral (ART) drugs has previously been associated with lipodystrophic syndrome, metabolic consequences, and neuropsychiatric complications. ART drugs include three main classes of protease inhibitors (PIs), nucleoside analog reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our previous work demonstrated that a high risk of hyperlipidemia was observed in HIV-1-infected patients who received ART drugs in Taiwan. Patients receiving ART drugs containing either Abacavir/Lamivudine (Aba/Lam; NRTI/NRTI), Lamivudine/Zidovudine (Lam/Zido; NRTI/NRTI), or Lopinavir/Ritonavir (Lop/Rit; PI) have the highest risk of hyperlipidemia. The aim of this study was to investigate the effects of Aba/Lam (NRTI/NRTI), Lam/Zido (NRTI/NRTI), and Lop/Rit (PI) on metabolic and neurologic functions in mice. Groups of C57BL/6 mice were administered Aba/Lam, Lam/Zido, or Lop/Rit, orally, once daily for a period of 4 weeks. The mice were then extensively tested for metabolic and neurologic parameters. In addition, the effect of Aba/Lam, Lam/Zido, and Lop/Rit on lipid metabolism was assessed in HepG2 hepatocytes and during the 3T3-L1 preadipocyte differentiation. Administration with Aba/Lam caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in leptin serum levels. Administration with Lop/Rit also caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in serum levels of total cholesterol, and HDL-c. Treatment of mice with Aba/Lam and Lop/Rit enhanced the lipid accumulation in the liver, and the decrease in AMP-activated protein kinase (AMPK) phosphorylation and/or its downstream target acetyl-CoA carboxylase (ACC) protein expression. In HepG2 hepatocytes, Aba/Lam, Lam/Zido, and Lop/Rit also enhanced the lipid accumulation and decreased phosphorylated AMPK and ACC proteins. In 3T3-L1 pre-adipocyte differentiation, Aba/Lam and Lop/Rit reduced adipogenesis by decreasing expression of transcription factor CEBPb, implicating the lipodystrophic syndrome. Our results demonstrate that daily oral administration of Aba/Lam and Lop/Rit may produce cognitive, motor, and metabolic impairments in mice, regardless of HIV-1 infection.

Carnosic acid impedes cell growth and enhances anticancer effects of carmustine and lomustine in melanoma.

Carnosic acid (CA), a major polyphenolic diterpene present in Rosmarinus officinalis, has been reported to have multiple functions, including antitumor activity. The MTT assay, BrdU incorporation, wound healing, and colony formation were used to detect melanoma B16F10 cell growth and proliferation. Flow cytometry was used for cell cycle detection. p21 and p27 expression was detected by Western blotting. B16F10 cell xenograft model was established, and treated with CA, carmustine (BCNU), or lomustine (CCNU). The present study found that CA exhibits significant growth inhibition and cell cycle arrest in melanoma B16F10 cells. We also found that CA triggers cell cycle arrest at G0/G1 phase, and enhances p21 expression. Additionally, CA can enhance BCNU- and CCNU-mediated cytotoxicity and cell cycle arrest in B16F10 cells. Finally, we found that CA inhibits tumor growth, and reduces the values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in vivo The present study study concluded that CA may be safe and useful as a novel chemotherapeutic agent.