Impact of hydroxyurea therapy on serum fatty acids of β-thalassemia patients

Introduction and objective

Fatty acids (FAs) influence cell and tissue metabolism, function, responsiveness to hormonal and other signals in addition to maintenance of membrane integrity of cells. β-Thalassemia is a prevalent inherited blood disorder characterized by abnormal red cell membrane structure and function. Induction of HbF by hydroxyurea (HU) is an enduring therapeutic intervention to manage this. Therefore, in the present study we have carried out the quantification of thirteen free fatty acids to disclose the prognosis of HU in β-thalassemia.

Methods

FAs quantification was carried out using GC–MRM–MS method in the serum of 98 cases of β-thalassemia patients and out of which samples from 34 patients were collected before and after treatment with HU in addition to healthy controls (n?=?31).

Results

Using the combination of random forest (RF) with GC–MRM–MS we were able to establish a classification and prediction model that can discriminate the β-thalassemia from healthy as well as from HU treated group. Docosanoic acid (C-22:0) was most significantly altered in β-thalassemia as compared to healthy at p-value of 8.3?×?10^?09 while erucic acid (C-22:1 Δ^cis-13) can be used as potential marker of HU prognosis because its level became significantly dissimilar at p-value of 3.7?×?10^?04 in same patients in response to HU. However, nervonic acid (C-24:1 Δ^cis-15) was found to be the key player in effectively separating three groups.

Conclusion

In inference, we have noticed that HU therapy also rectifies the serum fatty acid profile in addition to its reported affect i.e. HbF induction in β-thalassemia patients.

     

In vitro antiproliferative effects on human tumor cell lines of extracts from the Bangladeshi medicinal plant Aegle marmelos Correa.

In the present paper we show that extracts from Aegle marmelos Correa are able to inhibit the in vitro proliferation of human tumor cell lines, including the leukemic K562, T-lymphoid Jurkat, B-lymphoid Raji, erythroleukemic HEL, melanoma Colo38, and breast cancer MCF7 and MDA-MB-231 cell lines. Molecules present within the studied Aegle marmelos C. extracts were identified by gas-chromatography/mass-spectrometry analysis; three derivatives (butyl p-tolyl sulfide, 6-methyl-4-chromanone and butylated hydroxyanisole) were found to exhibit strong activity in inhibiting in vitro cell growth of human K562 cells. The antiproliferative activity of these compounds was found to be comparable to that of known antitumor agents, including cisplatin, chromomycin, cytosine arabinoside and 5-fluorouracil. In addition, the antiproliferative activity of butyl-p-tolyl sulfide, 6-methyl-4-chromanone and 5-methoxypsolaren was associated to activation of the differentiation pattern of K562 cells.     

Effect of aniline coupling on kinetic and thermodynamic properties of Fusarium solani glucoamylase

Purified glucoamylase (GA) from Fusarium solani was chemically modified by cross-linking with aniline hydrochloride in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) for 1 [aniline-coupled glucoamylase-1 (ACG-1)], 7 (ACG-7), and 13 min (ACG-13). The aniline coupling of GA had a profound enhancing effect on temperature, pH optima, and pK _a’s of active site residues. The specificity constants (K _cat/K _m) of native, ACG-1, ACG-7, and ACG-13 were 136, 244, 262, and 208 at 55°C for starch, respectively. The enthalpy of activation (ΔH*) and free energy of activation (ΔG*) for soluble starch hydrolysis were lower for the chemically modified forms compared to native GA. Proteolysis of ACGs by α-chymotrypsin and subtilisin resulted in activation.     

Point prevalence of gastrointestinal helminthiasis in ruminants in southern Punjab, Pakistan

The present study was carried out to determine the prevalence of gastrointestinal helminthiasis in ruminants in an irrigated area of lower Punjab (Pakistan). For this purpose, 100 faecal samples were collected from sheep, goats, cattle and buffaloes. Parasitological procedures including direct and indirect methods (sedimentation and floatation) and coproculture were used for the identification of helminths. The overall prevalence of helminthiasis was 51% in cattle, 47% in buffaloes, 62% in sheep and 52% in goats, with nematodes being the most common helminths. The prevalence of helminths was higher in young animals compared with adults in cattle (P < 0.0001), buffaloes (P < 0.0001), sheep (P < 0.059) and goats (P = 0.010). The prevalence of different species of helminths also varied in different age groups, with Toxocara vitulorum being higher in calves than adults both in cattle (P = 0.017) and buffaloes (P < 0.0001). Sex-wise prevalence of helminths was higher in males than females for buffaloes (P < 0.0001) and sheep (P = 0.014) in contrast to cattle and goats.     

Transient Expression Analysis of Agave sisalana Heat Shock Protein Gene (AsHSP70) in Model Species (Nicotiana benthamiana) under Heat Stress

Biology Bulletin - This study is aimed at investigating whether overexpression of the heat shock protein gene (AsHSP70) isolated from Agave sisalana will improve the heat stress tolerance in...     

Invivo inactivation of γ-aminobutyric acid-α-ketoglutarate transaminase by 4-amino-5-fluoropentanoic acid

Intraperitoneal injection into mice of varying concentrations of (S)-4-amino-5-fluoropentanoic acid ((S)-AFPA) produces a dose-dependent irreversible decrease in brain γ-aminobutyric acid-α-ketoglutaric acid aminotransferase (E.C. 2.6.1.19) activity. Concomitant with this inactivation is an increase in whole brain γ-aminobutyric acid (GABA) levels. Four hours after a dose of 100 mg/kg body weight of (S)-AFPA to mice, endogenous brain GABA concentrations increase to 16 times that of the untreated animals and the enzyme activity decreases to 20% that of the controls. The binding of (S)-AFPA to GABA receptors was more than three orders of magnitude poorer than for GABA itself.     

Human immunodeficiency virus type 1 Vpu protein induces degradation of chimeric envelope glycoproteins bearing the cytoplasmic and anchor domains of CD4: role of the cytoplasmic domain in Vpu-induced degradation in the endoplasmic reticulum.

The human immunodeficiency virus type 1 (HIV-1) Vpu protein is a transmembrane phosphoprotein which induces rapid degradation of CD4 in the endoplasmic reticulum (ER). To identify sequences in CD4 for Vpu-induced degradation, we generated four chimeric envelope glycoproteins having the ectodomain of HIV-1 gp160, the anchor domain of CD4, and 38, 25, 24, and 18 amino acids (aa) of the CD4 cytoplasmic domain. Using the vaccinia virus-T7 RNA polymerase expression system, we analyzed the expression of chimeric proteins in the presence and absence of Vpu. In singly transfected cells, the chimeric envelope glycoproteins having 38, 24, and 18 aa of the CD4 cytoplasmic domain were endoproteolytically cleaved and biologically active in the fusion of HeLa CD4+ cells. However, one of the chimeras having 25 aa of the CD4 cytoplasmic tail was retained in the ER using the transmembrane ER retention signal and was defective in membrane fusion. Furthermore, biochemical analyses of the coexpressing cells revealed that the Vpu protein induced degradation of the envelope glycoproteins having 38, 25, and 24 aa of the CD4 cytoplasmic tail and degradation occurred in the ER. Consequently, the fusion-competent glycoproteins did not induce the formation of syncytia in HeLa CD4+ cells expressing Vpu. However, the HIV-1 gp160 and chimeric envelope glycoprotein having the membrane-proximal 18 aa of the CD4 cytoplasmic tail were stable and fusion competent in cells expressing Vpu. In addition, we examined the stability of CD4 molecules in the presence of Vpu. Coexpression analyses revealed that the Vpu protein induced degradation of CD4 whereas mutant CD4 having the membrane-proximal 18 aa of the cytoplasmic domain was relatively stable in the presence of Vpu. Taken together, these studies have elucidated that the Vpu protein requires sequences or sequence determinants in the cytoplasmic domain of CD4 to induce degradation of the glycoproteins in the cell.     

Genetically engineered neural stem cells (NSCs) therapy for neurological diseases; state-of-the-art

Neural stem cells (NSCs) are multipotent stem cells with remarkable self-renewal potential and also unique competencies to differentiate into neurons, astrocytes, and oligodendrocytes (ODCs) and improve the cellular microenvironment. In addition, NSCs secret diversity of mediators, including neurotrophic factors (e.g., BDNF, NGF, GDNF, CNTF, and NT-3), pro-angiogenic mediators (e.g., FGF-2 and VEGF), and anti-inflammatory biomolecules. Thereby, NSCs transplantation has become a reasonable and effective treatment for various neurodegenerative disorders by their capacity to induce neurogenesis and vasculogenesis and dampen neuroinflammation and oxidative stress. Nonetheless, various drawbacks such as lower migration and survival and less differential capacity to a particular cell lineage concerning the disease pathogenesis hinder their application. Thus, genetic engineering of NSCs before transplantation is recently regarded as an innovative strategy to bypass these hurdles. Indeed, genetically modified NSCs could bring about more favored therapeutic influences post-transplantation in vivo, making them an excellent option for neurological disease therapy. This review for the first time offers a comprehensive review of the therapeutic capability of genetically modified NSCs rather than naïve NSCs in neurological disease beyond brain tumors and sheds light on the recent progress and prospect in this context.     

崇明东滩湿地芦苇种群内功能性状及生态对策变异分析

植物种群功能性状及生态对策变异对其自身环境适应能力及群落结构具有重要影响。该文基于崇明东滩湿地芦苇(Phragmites australis)种群内3个小种群不同发育时期分株集合的多项性状指标,分析了其性状及生态对策变异,并基于CSR、LHS生态对策体系,对各小种群的生态对策进行了排序。结果表明, 3个芦苇小种群的21项性状指标及C、R对策得分均存在显著差异。在LHS体系中,以比叶面积(11.5 mm2/mg)、株高(175 cm)和花序干质量(4 g)为分界线,可对3个小种群进行区分。处于生殖生长期的芦苇分株具有更大的植株大小、更高的叶片干物质含量及S对策得分,而处于营养生长期的分株则具有较小的植株大小、较大的比叶面积及R对策得分。总体而言,崇明东滩湿地3个芦苇小种群间及各小种群内处于不同生长发育阶段的分株集合间,都存在显著的性状差异及生态对策差异,且二者的差异模式基本吻合。芦苇种内性状及生态对策变异特征,可为该区芦苇种群的生态保育和恢复实践提供重要的理论参考和技术支撑。