Combination of sulfamethoxazole and selenium in anticancer therapy: a novel approach

Sulfonamides have been reported to possess substantial antitumor activity as they act as carbonic anhydrase inhibitors. In addition, selenium appears to have a protective effect at various stages of cancer due to its antioxidant property, enhanced carcinogen detoxification, inhibition of cell invasion, and by inhibiting angiogenesis. Here, in the present study we aimed to evaluate and synergize the cytotoxic activity of sulfonamide and selenium (SM+SE) as effective therapy in the treatment of DENA-induced HCC. Hepatocarcinogeneis was induced by a single intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg) in phosphate buffer. 30 Male Wistar rats used in this study were divided randomly into five equal groups (n = 6). DENA-administered animals showed significant alteration (p < 0.001) in liver-specific enzymes—glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and Alpha fetoproteins (AFP), and also induced severe histopathological changes in the hepatic tissues. Interestingly, treatment with (SE+SE) (SM 30 mg/kg + SE 3 mg/kg) significantly reduced (P < 0.001, P < 0.001, P < 0.001, P < 0.001) the elevated AFP, SGOT, SGPT, and ALP levels, respectively, suggesting that combination therapy of SM+SE has a potential to treat DENA-induced liver damage.     

Study of PKRBD in HCV genotype 3a infected patients in response to interferon therapy in Pakistani population

Background

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated.

Results

In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones.

Conclusions

The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.

     

CeO2 nanoparticles synthesized through green chemistry are biocompatible: In vitro and in vivo assessment

Widespread use of cerium oxide (CeO₂) nanoparticles (NPs) is found in almost all areas of research due to their distinctive properties. CeO₂ NPs synthesized via green chemistry have been characterized for antioxidant, phytochemical, and biological potential. Physical characterization through scanning electron microscopy, XRD, and TGA showed that the NPs are circular in shape, 20‐25 nm in size, and stable in a wide range of temperature. NPs display significant antioxidant (32.7% free radical scavenging activity) and antileishmanial (IC₅₀ 48 µg mL^?1) properties. In vitro toxicity tested against lymphocytes verified that NPs are biocompatible (99.38% viability of lymphocytes at 2.5 μg mL^?1). In vivo toxicity experiments showed no harmful effects on rat serum chemistry and histology of various organs and did not even change the concentration of antioxidative enzymes, total protein contents, lipid peroxidation, and nitrosative stress. These observations are in line with the statement that plant‐based synthesis of CeO₂ NPs lessens or nullifies in vitro and in vivo toxicity and hence CeO₂ NPs are regarded as a safe and biocompatible material to be used in drug delivery.     

Recreating a functional ancestral archosaur visual pigment

The ancestors of the archosaurs, a major branch of the diapsid reptiles, originated more than 240 MYA near the dawn of the Triassic Period. We used maximum likelihood phylogenetic ancestral reconstruction methods and explored different models of evolution for inferring the amino acid sequence of a putative ancestral archosaur visual pigment. Three different types of maximum likelihood models were used: nucleotide-based, amino acid-based, and codon-based models. Where possible, within each type of model, likelihood ratio tests were used to determine which model best fit the data. Ancestral reconstructions of the ancestral archosaur node using the best-fitting models of each type were found to be in agreement, except for three amino acid residues at which one reconstruction differed from the other two. To determine if these ancestral pigments would be functionally active, the corresponding genes were chemically synthesized and then expressed in a mammalian cell line in tissue culture. The expressed artificial genes were all found to bind to 11-cis-retinal to yield stable photoactive pigments with lambda(max) values of about 508 nm, which is slightly redshifted relative to that of extant vertebrate pigments. The ancestral archosaur pigments also activated the retinal G protein transducin, as measured in a fluorescence assay. Our results show that ancestral genes from ancient organisms can be reconstructed de novo and tested for function using a combination of phylogenetic and biochemical methods.     

Interactions among oscillatory pathways in NF-kappa B signaling

Background  

Sustained stimulation with tumour necrosis factor alpha (TNF-alpha) induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B) system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer) and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways.     

Time-resolved photointermediate changes in rhodopsin glutamic acid 181 mutants

The role of glutamic acid 181 in the bovine rhodopsin retinylidene chromophore pocket was studied by expressing E181 mutants in COS cells and measuring, as a function of time, the absorbance changes produced after excitation of lauryl maltoside pigment suspensions with 7 ns laser pulses. All mutants studied except E181D showed accelerated decay of bathorhodopsin compared to wild type. Even for E181D, an anomalously large blue shift was observed in the absorption spectrum of the bathorhodopsin decay product, BSI. These observations support the idea that E181 plays a significant role in the earliest stages of receptor activation. E181 mutations have a pronounced effect on the decay of the lumirhodopsin photointermediate, primarily affecting the size of the red shift that occurs in the lumirhodopsin I to lumirhodopsin II transition that takes place on the 10 micros time scale after wild-type photoexcitation. While the spectral change that occurs in the lumirhodopsin I to lumirhodopsin II transition in wild-type rhodopsin is very small ( approximately 2 nm), making it difficult to detect, it is larger in E181D ( approximately 6 nm), making it evident even in the lower signal-to-noise ratio measurements possible with rhodopsin mutants. The change seen is even larger for the E181F mutant where significant amounts of a deprotonated Schiff base intermediate are produced with the 10 micros time constant of lumirhodopsin II formation. The E181Q mutant shows lumirhodopsin decay more similar to wild-type behavior, and no lumirhodopsin I to lumirhodopsin II transition can be resolved. The addition of chloride ion to E181Q increases the lumirhodopsin I-lumirhodopsin II spectral shift and slows the deprotonation of the Schiff base. The latter result is consistent with the idea that a negative charge at position 181 contributes to protonated Schiff base stability in the later intermediates.     

Complex genetics controls natural variation among seed quality phenotypes in a recombinant inbred population of an interspecific cross between Solanum lycopersicum × Solanum pimpinellifolium

Seed quality in tomato is associated with many complex physiological and genetic traits. While plant processes are frequently controlled by the action of small‐ to large‐effect genes that follow classic Mendelian inheritance, our study suggests that seed quality is primarily quantitative and genetically complex. Using a recombinant inbred line population of Solanum lycopersicum × Solanum pimpinellifolium, we identified quantitative trait loci (QTLs) influencing seed quality phenotypes under non‐stress, as well as salt, osmotic, cold, high‐temperature and oxidative stress conditions. In total, 42 seed quality traits were analysed and 120 QTLs were identified for germination traits under different conditions. Significant phenotypic correlations were observed between germination traits under optimal conditions, as well as under different stress conditions. In conclusion, one or more QTLs were identified for each trait with some of these QTLs co‐locating. Co‐location of QTLs for different traits can be an indication that a locus has pleiotropic effects on multiple traits due to a common mechanistic basis. However, several QTLs also dissected seed quality in its separate components, suggesting different physiological mechanisms and signalling pathways for different seed quality attributes.     

Prevalence of Chlamydia trachomatis infections in Karachi, Pakistan.

An epidemiological study was carried out to determine the prevalence of Chlamydia infections in adult females by enzyme immunoassay and microscopic examination of Giemsa-stained smears. Endocervical swabs were collected from 126 females attending OB/GYN ward at Abbasi Shaheed Hospital, Karachi. 13.5% of 126 females tested were positive by enzyme immunoassay and only 5.6% were positive by the Giemsa-staining method. The infection rate among pregnant and nonpregnant women with urinogenital problems were 11.8% and 14.7%, respectively. The majority of females complained of excessive cervical discharge and pain in the lower abdomen. A high prevalence of infection in normal pregnant women (18.2%) indicates the asymptomatic nature of this infection.