Being overweight and obese increases suicide risk, the severity of depression, and the inflammatory response in adolescents with major depressive disorders.

Background: There is a bidirectional relationship between obesity and depression. We investigated whether the coexistence of obesity and depression increases the risk of having severe depression and a high suicide risk in adolescents with major depressive disorder (MDD). Additionally, we explored the potential mechanisms linking the coexistence of obesity and depression to worse outcomes in these patients. Methods: The odds of high suicide risk and severe depression were compared among MDD patients based on different body mass index (BMI) groups. Complete blood count (CBC) parameters, inflammatory ratios (neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], and platelet-lymphocyte ratio [PLR]), and cytokine levels (IFN-γ, IL-1ß, IL-6, IL-8, MCP-1, TNF-α, and TGF-ß1) were evaluated across BMI groups. Additionally, Pearson correlation coefficients (r) were assessed to understand the relationships between the 8Q and 9Q scores, CBC parameters, inflammatory ratios, cytokine levels, and BMI. Results: A total of 135 antidepressant-naive adolescents with MDD were included. Overweight and obese MDD patients had higher odds of having high suicide risk and severe depression than lean individuals. Furthermore, they exhibited significantly higher white blood cell (WBC), and neutrophil counts. The NLR tended to be higher in obese MDD patients than in leans. Overweight and obese MDD patients had elevated levels of interleukin (IL)-1ß and IL-6 compared to lean individuals, while TGF-ß1 levels appeared to decline as body weight increased. BMI showed weak positive correlations with 8Q score, WBC count, neutrophil count, monocyte count, platelet count, neutrophil percentage, and NLR, and a weak negative correlation with lymphocyte percentage. The 8Q score displayed weak positive correlations with BMI, neutrophil percentage, monocyte percentages, NLR, and MLR, and a weak negative correlation with lymphocyte percentage. Conclusion: The findings suggest that coexistence of overweight or obesity with depression heightened inflammatory responses, leading to worse outcomes and increased suicide risk in adolescents MDD patients.

Long-Term Persistence of Chikungunya Virus-Associated Manifestations and Anti-Chikungunya Virus Antibody in Southern Thailand: 5 Years After an Outbreak in 2008-2009.

Chikungunya fever, a disease caused by chikungunya virus (CHIKV), reemerged and affected over 52,000 people in southern Thailand in 2008 and 2009. The CHIKV strain involved in this outbreak was the East Central South African (ECSA) strain with the E1-A226V mutation. The prevalence of CHIKV-associated chronic discomfort varied by virus lineage. This retrospective cohort study aims to describe the CHIKV-related symptoms persisting in CHIKV-affected patients, related factors, and the presence of anti-CHIKV immunoglobulin G (IgG) antibodies 5 years after the onset of disease. From 5,344 of the study population screened, a total of 89 affected patients reported persistent arthralgia 5 years after the disease onset (nonrecovery rate = 1.7%). Of the 141 affected patients enrolled, 122 cases (86.5%; 77 cases with persistent arthralgia and 45 cases of fully recovered) still had detectable levels of anti-CHIKV IgG antibodies. Long-term persistence of chronic joint symptoms is associated with the severity of the disease during the initial phase of the infection, but not gender, age, or comorbidities. The common manifestations were arthralgia (75.3%), morning joint stiffness (39.0%), muscle pain (19.5%), and occasional joint swelling (16.9%). Chronic joint symptoms could occur in either a fluctuating or a persistent manner and usually caused moderate pain. The joints affected were mainly fingers (71.4%), wrists (51.9%), and knees (50.6%). Most patients had polyarthralgia with symmetrical joint involvement. In some cases with persistent arthralgia, atypical manifestations, including severe depression with suicide attempts, severe weight loss, and severe hair loss, were found, and some patients still experienced severe joint pain.

Proinflammatory Cytokines and Chemokines as Biomarkers of Persistent Arthralgia and Severe Disease After Chikungunya Virus Infection: A 5-Year Follow-Up Study in Southern Thailand.

Chikungunya fever is a re-emerging viral disease caused by chikungunya virus (CHIKV). The disease is generally self-limiting, but chronic arthralgia/arthritis may persist for months or years. We evaluated the expression of 12 cytokines/chemokines and matrix metalloproteinases (MMP)-1 and MMP-3 using enzyme-linked immunosorbent assays (ELISAs) and compared among patients who still had arthralgia (persistent arthralgia), patients who had fully recovered, and healthy controls. There was a significant increase in interleukin (IL)-1ß, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), MMP-1, and MMP-3 levels in patients with persistent arthralgia in comparison to healthy controls (p < 0.05) and a significant increase in tumor necrosis factor-alpha (TNF-α), MMP-1, and MMP-3 levels in patients with persistent arthralgia in comparison to patients who had fully recovered (p < 0.05). Interferon (IFN)-γ, IL-6, and transforming growth factor beta (TGF-ß) levels tended to be increased in patients with chronic CHIKV-induced arthritis compared with fully recovered. TNF-α, IL-12, and MCP-1 levels were elevated (p < 0.05), whereas regulated on activation, normal T cell expressed and secreted (RANTES) levels were decreased in patients with severe pain compared with patients with nonsevere pain (p < 0.05). IFN-γ, IL-1ß, IL-6, and IL-8 levels tended to be elevated in patients with severe pain compared with patients with nonsevere pain. We proposed a role played by TNF-α, IL-6, IL-8, and MCP-1 in persistent arthralgia or chronic disease through the activation of MMP-1 and MMP-3. The increase in TNF-α, IL-12, and MCP-1 levels (and the tendency toward an increase in IFN-γ, IL-1ß, IL-6, and IL-8 levels) in patients with severe pain compared with patients with nonsevere pain suggests the role of these inflammatory markers in chronic disease and severity of the disease.

Ivy gourd (Coccinia grandis L. Voigt) root suppresses adipocyte differentiation in 3T3-L1 cells.

BACKGROUND: Ivy gourd (Coccinia grandis L. Voigt) is a tropical plant widely distributed throughout Asia, Africa, and the Pacific Islands. The anti-obesity property of this plant has been claimed but still remains to be scientifically proven. We therefore investigated the effects of ivy gourd leaf, stem, and root on adipocyte differentiation by employing cell culture model. METHODS: Dried roots, stems, and leaves of ivy gourd were separately extracted with ethanol. Each extract was then applied to 3T3-L1 pre-adipocytes upon induction with a mixture of insulin, 3-isobutyl-1-methylxanthine, and dexamethasone, for anti-adipogenesis assay. The active extract was further fractionated by a sequential solvent partitioning method, and the resulting fractions were examined for their abilities to inhibit adipogenesis in 3T3-L1 cells. Differences in the expression of adipogenesis-related genes between the treated and untreated cells were determined from their mRNA and protein levels. RESULTS: Of the three ivy gourd extracts, the root extract exhibited an anti-adipogenic effect. It significantly reduced intracellular fat accumulation during the early stages of adipocyte differentiation. Together with the suppression of differentiation, expression of the genes encoding PPARγ, C/EBPα, adiponectin, and GLUT4 were down-regulated. Hexane-soluble fraction of the root extract also inhibited adipocyte differentiation and decreased the mRNA levels of various adipogenic genes in the differentiating cells. CONCLUSIONS: This is the first study to demonstrate that ivy gourd root may prevent obesity based mainly on the ability of its active constituent(s) to suppress adipocyte differentiation in vitro. Such an inhibitory effect is mediated by at least down-regulating the expression of PPARγ-the key transcription factor of adipogenesis in pre-adipocytes during their early differentiation processes.

Physicochemical performances of indomethacin in cholesteryl cetyl carbonate liquid crystal as a transdermal dosage.

A transdermal formulation of indomethacin (IMC) was developed by incorporation into cholesteryl cetyl carbonate (CCC). The liquid crystalline phase properties of the IMC-CCC mixture were detected by polarized light microscopy and differential scanning calorimetry. A low drug loading was obtained (1-5 %) similar to that used in conventional topical IMC in a clinical setting. A controlled release of IMC was found over 12 h. A low amount of IMC in 1 % IMC-CCC permeated the stratum corneum. Further formulation development has been carried out by the addition of lauryl alcohol into 5 % IMC-CCC mixture it was found that the permeation of IMC was significantly improved to 45 % within 24 h.

Bioactivity and toxicity studies of amphotericin B incorporated in liquid crystals.

The main objective of the present work was to evaluate the bioactivity and safety of amphotericin B-liquid crystal mixtures (AmB-LC). The effects of liquid crystal (LC) materials and AmB-LC ratios on bioactivity and toxicity to respiratory cell lines were investigated. The formation of AmB-LC mixtures did not change the physical properties of LC when the AmB loading was not more than a 1:3 mole ratio (25%). The exposure of respiratory cell lines to LC did not generate any toxicity (2.5-80 µg/mL). The inhibitory activity of AmB in all liquid crystal formulations (cholesteryl palmityl carbonate: CPC, dicholesteryl carbonate: DCC and sodium cholesteryl carbonate: SCC) on fungi was significantly enhanced when compared to that of the same amount of pure AmB. However, their toxicity to respiratory related cells and red blood cells was significantly decreased. This could be a huge advantage in clinical applications as there is more possibility for dose adjustments. The exposure of small airway epithelial cells (SAEC) and alveolar macrophages (AMs NR8383) to liquid crystals had no significant detrimental effects at doses of between 2.5 and 80 µg/mL (viability was always over 80%). The production of toxic cytokines and inflammatory mediators, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and nitric oxide (NO), after treatment with AmB in liquid crystals at concentrations of between 2 and 32 µg/mL was significantly reduced by about a 1000-fold compared to that generated by lipopolysaccharide (LPS).

Carbazoles and coumarins from Clausena harmandiana stimulate glucose uptake in L6 myotubes.

Two carbazoles (compounds 1 and 2) and one coumarin (compound 8) from Clausena harmandiana exhibited significant glucose uptake activity in L6 myotubes in a time and dose dependent manner. In addition, compounds 2 and 8 were inhibited by p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinases, respectively.