Effects of CT-Xp Gene Knock down in Melanoma Cell Lines

Cancer/testis (CT) genes are encoded by genes that are normally expressed only in the human germ line but which are activated in various malignancies. CT proteins are frequently immunogenic in cancer patients and their expression is highly restricted to tumors. They are thus important targets for anticancer immunotherapy. In several different tumor types, the expression of CT-X genes is associated with advanced disease and poor outcome, indicating that their expression might contribute to tumorigenesis. CT-X genes encoding members of the MAGE protein family on Xq28 have been shown to potentially influence the tumorigenic phenotype. We used small interfering RNA (siRNA) to investigate whether CT-X mapping to the short arm of the X-chromosome might also have tumorigenic properties and therefore be potentially targeted by functional inhibitors in a therapeutic setting. siRNAs specific to GAGE, SSX and XAGE1 were used in cell proliferation, migration and cell survival assays using cell lines derived from melanoma, a tumor type known to present high frequencies of expression of CT antigens. We found that of these, those specific to GAGE and XAGE1 most significantly impeded melanoma cell migration and invasion and those specific to SSX4 and XAGE1 decreased the clonogenic survival of melanoma cells. Our results suggest that GAGE, XAGE1 and SSX4 might each have a role in tumor progression and are possible therapeutic targets for the treatment of melanoma and other malignancies.     

Maculosin,a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

ContextStreptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities.ObjectiveThis study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed.Materials and methodsThe compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay.ResultsEthyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 µg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12–KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C₁₄H₁₆N₂O₃ as determined by the [M + H]⁺ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC₅₀, 2.16 ± 0.05 µg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC₅₀, 4.8 ± 0.05 µg/mL). No toxicity was observed for maculosin (LD₅₀, <128 µg/mL) in brine shrimp lethality assay (BSLA) up to the compound’s antioxidant activity (IC₅₀) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD₅₀ value of 8.63 ± 0.15 µg/mL.ConclusionsMaculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.     

Pediatric Scrub typhus in South Sikkim

We present five cases of paediatric Scrub typhus from Community Health Centre, Namchi, South Sikkim emphasize timely diagnosis of scrub typhus for appropriate management. Response to doxycycline was good, with fever subsiding within 48-72 hrs of starting the treatment. Four out of five cases completely recovered once appropriate medication was given.     

An open, randomized, comparative study of efficacy and safety of risperidone and haloperidol in schizophrenia.

Objectives: In the last decade there have been numerous randomized controlled trials comparing the efficacy and safety of second generation antipsychotics and conventional antipsychotics in the treatment of schizophrenia, but most of them have been conducted in the western population. This study compared the efficacy and safety of risperidone versus haloperidol in the Nepalese context, in order to add on to the very few literatures available on this topic in the South East Asia region and compare them. Methods: Patients with the diagnosis of schizophrenia were randomly assigned to receive risperidone 4-6 milligrams (mg) per day and haloperidol 10-20 mg per day, and were followed up for 6 weeks. Assessment were done on the day of the diagnostic interview and days 7, 14, 28 and 42 (end point). During the assessment periods Positive and Negative Syndrome Scale (PANSS) was administered to monitor the progress in psychopathology and Udvalg for Kliniske Undersogelser (UKU) side effects rating scale was applied to rate the treatment emergent adverse effects. Results: Both risperidone and haloperidol were associated with substantial baseline- to- endpoint reduction in symptom severity. After one week of treatment, the improvement in schizophrenia with risperidone was significantly better than haloperidol in terms of PANSS- total Score (-45.4 versus -29.5), negative subscale score (-14.3 versus -6.68) and general psychopathology subscale score (-20.9 versus -13.7). At the end point of the study, the benefit was maintained in total score (-52.1 versus -43.1), though the negative subscale score still showed tendency for greater improvement in psychopathology with risperidone. The side effects profile did not show significant differences except in extrapyramidal symptoms. Thirty-eight percent of risperidone treated patients had to resort to anti-parkinsonian treatment compared to 78% in haloperidol treatment group. Conclusion: Similar to the studies in the western countries, Asia and Indian subcontinent, both risperidone and haloperidol were effective in the reduction of psychopathological symptoms in this group of Nepalese population with the diagnosis of schizophrenia. However, risperidone was quicker and better then haloperidol and risperidone had a better safety profile. This is important, because extrapyramidal side effects of neuroleptics are responsible for non-compliance and increased cost in terms of us of anti-parkinsonian medication. Key words: schizophrenia, antipsychotic, risperidone, haloperidol, positive and negative syndrome scale (PANSS).     

Lung metastasis from renal cell carcinoma 16 years after nephrectomy: A case report and review of the literature

Renal cell carcinoma can have lung metastasis even after a long interval of radical nephrectomy (16 years after nephrectomy in our case). If any pulmonary nodule is diagnosed with a history of RCC, pulmonary metastasis of RCC should be suspected and should be appropriately treated.     

An NLRP3 inflammasome–triggered Th2-biased adaptive immune response promotes leishmaniasis

Leishmaniasis is a major tropical disease that can present with cutaneous, mucocutaneous, or visceral manifestation and affects millions of individuals, causing substantial morbidity and mortality in third-world countries. The development of a Th1-adaptive immune response is associated with resistance to developing Leishmania major (L. major) infection. Inflammasomes are key components of the innate immune system that contribute to host defense against bacterial and viral pathogens; however, their role in regulating adaptive immunity during infection with protozoan parasites is less studied. Here, we demonstrated that the NLRP3 inflammasome balances Th1/Th2 responses during leishmaniasis. Mice lacking the inflammasome components NLRP3, ASC, or caspase 1 on a Leishmania-susceptible BALB/c background exhibited defective IL-1β and IL-18 production at the infection site and were resistant to cutaneous L. major infection. Moreover, we determined that production of IL-18 propagates disease in susceptible BALB/c mice by promoting the Th2 cytokine IL-4, and neutralization of IL-18 in these animals reduced L. major titers and footpad swelling. In conclusion, our results indicate that activation of the NLRP3 inflammasome is detrimental during leishmaniasis and suggest that IL-18 neutralization has potential as a therapeutic strategy to treat leishmaniasis patients.