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Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

lbgBackground and Objective:l/bg Primary Nonsyndromic Vesicoureteral Reflux (PVUR) is a widespread genetic malformation and considered a prevalent Congenital Abnormality of the Kidney and Urinary Tract (CAKUT). Mutations in the ligPAX2 l/iggene have been associated with abnormalities in the kidney extending from CAKUT to oncogenic processes. The present study analyzes the ligPAX2l/ig polymorphisms and their association with primary VUR in Saudi children patients from the Taif governorate. lbgMaterials and Methods:l/bg Fifteen children with primary VUR were identified and screened for gene mutations in the ligPAX2l/ig gene by direct sequencing method of purified Polymerase Chain Reaction (PCR) products of all exons to elucidate the correlation between ligPAX2l/ig gene and VUR. lbgResults:l/bg Seven new variants have been defined. Three polymorphic missense variants in homozygous genotype form were found in intron 8 and detected in eight patients, One missense mutation was found in exon 10 in the site of transactivation domain and detected in ten patients and ligin-silicol/ig analysis predicted it as a pathogenic one, Three mutations were found in exon 11 and detected in all patients as a compound homozygous. lbgConclusion:l/bg ligPAX2l/igis important for normal kidney development and mutations in the gene possibly lead to disturbance in the protein structure and could be non-functional thus mutations in ligPAX2l/ig may be one of the causes of PVUR in Saudi Arabia. Further investigation is necessary to understand the aetiology of disease and maybe other genes implicated in VUR.

lt;bgt;Background and Objective:lt;/bgt; Primary Nonsyndromic Vesicoureteral Reflux (PVUR) is a widespread genetic malformation and considered a prevalent Congenital Abnormality of the Kidney and Urinary Tract (CAKUT). Mutations in thelt;igt;PAX2lt;/igt;gene have been associated with abnormalities in the kidney extending from CAKUT to oncogenic processes. The present study analyzes thelt;igt;PAX2lt;/igt; polymorphisms and their association with primary VUR in Saudi children patients from the Taif governorate.lt;bgt;Materials and Methods:lt;/bgt; Fifteen children with primary VUR were identified and screened for gene mutations in thelt;igt;PAX2lt;/igt; gene by direct sequencing method of purified Polymerase Chain Reaction (PCR) products of all exons to elucidate the correlation betweenlt;igt;PAX2lt;/igt; gene and VUR.lt;bgt;Results:lt;/bgt; Seven new variants have been defined. Three polymorphic missense variants in homozygous genotype form were found in intron 8 and detected in eight patients, One missense mutation was found in exon 10 in the site of transactivation domain and detected in ten patients andlt;igt;in-silicolt;/igt; analysis predicted it as a pathogenic one, Three mutations were found in exon 11 and detected in all patients as a compound homozygous.lt;bgt;Conclusion:lt;/bgt;lt;igt;PAX2lt;/igt;is important for normal kidney development and mutations in the gene possibly lead to disturbance in the protein structure and could be non-functional thus mutations inlt;igt;PAX2lt;/igt; may be one of the causes of PVUR in Saudi Arabia. Further investigation is necessary to understand the aetiology of disease and maybe other genes implicated in VUR.

Cropping systems in the Level Barind Tract (LBT) of Bangladesh are highly diverse, as Transplanted (T.) Aman and Boro (T. Boro) rice are a common practice in the area. Although. T. Aman is generally cultivated in the rainy (monsoon) season, but the T. Boro rice is the intensive irrigation-based winter rice with high establishment costs as a result of exhaustive tillage and high labours for transplanting of seedlings. Furthermore, pumping of a large amount of irrigation during T. Boro cultivation declines the level of groundwater, which is not environmentally friendly nor cost-effective. Therefore, the replacement of the T. Boro rice from the cropping pattern in the LBT area is the major concern of policymakers. In this context, a replicated three to four crop-based cropping systems (CS) field trial was conducted in LBT of Gaibandha, Bangladesh for consecutive three years (2018–2020) to evaluate productivity, profitability and sustainability of the multiple crop-based cropping systems. Among these CS, existing three crops based CS, CS1: T. Aman–Potato–T. Boro (introduction of the local potato in the existing cropping system) were compared with four crops based CS2: T. Aman–Potato–Cucumber–T. Aus (Introduction of high yielding potato, cucumber and T. Aus as an improved cropping system). After two years of observations, significantly higher system productivity (rice equivalent yield, REY) was found in the improved CS2 than that of existing CS1 in both years (two years’ average 49% or 11.1 t ha−1). As a result of the introduction of the high yielding potato, cucumber and T. Aus rice instead of the T. Boro rice. The CS2 was also found profitable as compared to the CS1 in terms of higher gross margin (by 74%), net return (double) and benefit-cost ratio (BCR) (1.69 vs. 1.44) due to higher gross return with slightly higher (by 28%) production cost. It is due to farmers received higher prices for potato, cucumber and two rice crops in the improved CS2 than the existing CS1. On the other hand, protein and energy output was lower (by 17% and 9%, respectively) in the CS2 than the existing CS1, due to the less content of protein and energy value in the vegetable cucumber. The results of the study revealed that crops diversification in the existing T. Boro based CS with high yielding potato, cucumber, and T. Aus rice, improved the system productivity, profitability and sustainability, which lead to improve the food security of the increasing population and also reduce the adverse effect on the environment.

Alternaria species, mainly air-borne fungi, affect potato plants, causing black spots symptoms. Morphological identification, pathogenicity assessment, and internal transcribed spacer (ITS) molecular identification confirmed that all isolates were Alternaria alternata. The annotated sequences were deposited in GenBank under accession numbers MN592771–MN592777. HPLC analysis revealed that the fungal isolates KH3 (133,200 ng/g) and NO3 (212,000 ng/g) produced higher levels of tenuazonic acid (TeA) and alternariol monomethyl ether (AME), respectively. Beet ethanol extract (BEE) and beet methanol extract (BME) at different concentrations were used as antimycotoxins. BME decreased the production of mycotoxins by 66.99–99.79%. The highest TeA reduction rate (99.39%) was reported in the KH3 isolate with 150 µg/mL BME treatment. In comparison, the most effective AME reduction rate (99.79%) was shown in the NO3 isolate with 150 µg/mL BME treatment. In the same way, BEE application resulted in 95.60–99.91% mycotoxin reduction. The highest TeA reduction rate (99.91%) was reported in the KH3 isolate with 150 µg/mL BEE treatment, while the greatest AME reduction rate (99.68%) was shown in the Alam1 isolate with 75 µg/mL BEE treatment. GC-MS analysis showed that the main constituent in BME was the antioxidant compound 1-dodecanamine, n,n-dimethyl with a peak area of 43.75%. In contrast, oxirane, methyl- (23.22%), hexadecanoic acid, methyl ester (10.72%), and n-hexadecanoic acid (7.32%) were the main components in BEE found by GC-MS. They are probably antimicrobial molecules and have an effect on the mycotoxin in general. To our knowledge, this is the first study describing the antimycotoxigenic activity of beet extracts against A. alternata mycotoxins-contaminated potato crops in Egypt, aimed to manage and save the environment.

Background and objective Radiation exposure can cause several harmful effects in biological systems due to free radical production. Several antioxidants have been tested as potential hepatoprotective agents against ionizing radiation as they lower oxidative stress in normal cells induced by Reactive Oxygen Species (ROS). The present study was conducted to evaluate the possible ameliorative effects of Juniperus phoenicea L. Materials and methods Aqueous leaves extract on different biochemical and histopathological parameters against whole body gamma-irradiation-induced oxidative stress, organ dysfunction and metabolic disturbances in experimental Swiss Albino rats. After a single dose of gamma-radiation (6 Gy), there was a significant reduction in albumin, total protein and globulin levels and a significant increase in the liver enzymes (ALT, AST, ALP and GGT) and lipid profile parameters (cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) in gamma-irradiated rats unlike in normal controls. Results The gamma-irradiated rats pre-treated with J. phoenicea leaf extracts, however, showed a significant increase in albumin, total protein and globulin levels and a significant reduction in liver enzymes and lipid profile parameters as opposed to the untreated ones. The gamma-irradiated rats showed toxic changes in the liver, whereas, the rats pre-treated with J. phoenicea leaves extract demonstrated a protective effect. Additionally, gamma- irradiation caused myocardial degenerative changes, interstitial edema between muscle fibers, necrosis and inflammatory cells infiltration and fibrotic and cellular damages to the heart, but J. phoenicea leaves extract were found to ameliorate the gamma-irradiation-induced changes in the heart. Conclusion The results suggested that treatment with J. phoenicea leaves extract is possibly safe and can ameliorate gamma-irradiation-induced oxidative damage and tissue injury in rats. The leaves of J. phoenicea could serve as a potential source of therapeutic antioxidants.

Tobacco mosaic virus (TMV) causes severe damage and economic losses of tomato in crop yield production and quality worldwide. Tomato plants infected with TMV usually show a mosaic pattern and chlorosis symptoms that result from affected chloroplasts. To elucidate tomato–TMV interactions, the transcriptional profiles of tomato tissues at different time intervals were analysed using a differential display-polymerase chain reaction technique. Compared to mock-inoculated plants, and based on gene expression changes in tomato plants, the representative down- and up-regulated genes were selected for further analysis. The Basic Local Alignment Search Tool at the National Center for Biotechnology Information (NCBI-BLAST) analysis revealed that the three up-regulated gene transcripts at 15 days post-inoculation were coding for chloroplast (MG565980 and MG565979) and kinesin-like proteins (MG565981). Additionally, the down-regulated gene was a chloroplast-related gene (MG565978). Interestingly, the two chloroplast genes, MG565978 and MG565980, shared more than 96% sequence identity, and their transmembrane profiles were nearly identical. On the other hand, many protein kinase C phosphorylation, casein kinase II phosphorylation and N-myristoylation sites were detected within the MG565981 gene. Moreover, the high similarity between the kinesin gene and many Arabidopsis defensin genes indicated that it might play an important role in the plant defence system against TMV infection. It should be stressed that studies of the pathways in which chloroplast and kinesin-like protein genes are involved may elucidate the mechanisms of tomato tolerance to viral infection and can lead us to a more comprehensive understanding of tomato–TMV interactions.

Purpose Short stature affects approximately 2%-3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene (SHOX) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. Methods We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Results A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX. Conclusion In Saudi Arabia ISS patients, rather than SHOX, it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

Purpose Short stature affects approximately 2%–3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene (SHOX) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. Methods We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Results A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX. Conclusion In Saudi Arabia ISS patients, rather than SHOX, it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

Mutations in fibrillin-1 lead to Marfan syndrome and some related genetic disorders. Many of the more than 600 mutations currently known in fibrillin-1 eliminate or introduce cysteine residues in epidermal growth factor-like modules. Here we report structural and functional consequences of three selected cysteine mutations (R627C, C750G, and C926R) in fibrillin-1. The mutations have been analyzed by means of recombinant polypeptides produced in mammalian expression systems. The mRNA levels for the mutation constructs were similar to wild-type levels. All three mutated polypeptides were secreted by embryonic kidney cells (293) into the culture medium. Purification was readily feasible for mutants R627C and C750G, but not for C926R, which restricted the availability of this mutant polypeptide to selected analyses. The overall folds of the mutant polypeptides were indistinguishable from the wild-type as judged by the ultrastructural shape, CD analysis, and reactivity with a specific antibody sensitive for intact disulfide bonds. Subtle structural changes caused by R627C and C750G, however, were monitored by proteolysis and heat denaturation experiments. These changes occurred in the vicinity of the mutations either as short range effects (R627C) or both short and long range effects (C750G). Enhanced proteolytic susceptibility was observed for R627C and C750G to a variety of proteases. These results expand and further strengthen the concept that proteolytic degradation of mutated fibrillin-1 might be an important potential mechanism in the pathogenesis of Marfan syndrome and other disorders caused by mutations in fibrillin-1.

Microfibrils are essential elements in elastic and nonelastic tissues contributing to homeostasis and growth factor regulation. Fibrillins form the core of these multicomponent assemblies. Various human genetic disorders, the fibrillinopathies, arise from mutations in fibrillins and are frequently associated with aberrant microfibril assembly. These disorders include Marfan syndrome, Weill–Marchesani syndrome, Beals syndrome, and others. Although homotypic and heterotypic fibrillin self-interactions are considered to provide critical initial steps, the detailed mechanisms for microfibril assembly are unknown. We show here that the C-terminal recombinant half of fibrillin-1 assembles into disulfide-bonded multimeric globular structures with peripheral arms and a dense core. These globules are similar to the beaded structures observed in microfibrils isolated from tissues. Only these C-terminal fibrillin-1 multimers interacted strongly with the fibrillin-1 N terminus, whereas the monomers showed very little self-interaction activity. The multimers strongly inhibited microfibril formation in cell culture, providing evidence that these recombinant assemblies can also interact with endogenous fibrillin-1. The C-terminal self-interaction site was fine-mapped to the last three calcium-binding EGF domains in fibrillin-1. These results suggest a new mechanism for microfibril formation where fibrillin-1 first oligomerizes via its C terminus before the partially or fully assembled bead-like structures can further interact with other beads via the fibrillin-1 N termini.

Autoantibodies against short recombinant fragments of fibrillin-1 produced in bacterial expression systems have been found in tight-skin mouse, systemic sclerosis, mixed connective tissue disease, and primary pulmonary hypertension syndrome. In patients with scleroderma, the frequency of anti-fibrillin-1 antibodies was 42% in Caucasians. Until now it has been unclear whether this immune response has a primary function in disease pathogenesis or is a secondary phenomenon. In the present study we analyzed the frequency of autoantibodies against two overlapping recombinant polypeptides spanning the N-terminal and C-terminal halves of human fibrillin-1, which were produced in human embryonic kidney (HEK-293) cells. Correct three-dimensional structures of the recombinant fibrillin-1 polypeptides were shown by electron microscopy and immunoreactivity with antibodies. Screening of fibrillin-1 antibodies was performed in 41 sera from systemic sclerosis patients and in 44 healthy controls with a Caucasian background. Microtiter plates were coated with the recombinant polypeptides of fibrillin-1 and incubated with 1:100 diluted sera. Positive binding was defined as being more than 2 SD above the mean of the control group. ELISAs showed that none of the sera of patients with systemic sclerosis contained autoantibodies against the N-terminal or C-terminal recombinant fibrillin-1 polypeptide. The data show the absence of autoantibodies against recombinant fibrillin-1 protein in Caucasian systemic sclerosis patients. Because the correct three-dimensional folding of the recombinant proteins has been substantiated by several independent methods, we conclude that autoantibodies against correctly folded fibrillin are not a primary phenomenon in the pathogenesis of systemic sclerosis.