Transcription factor 7 like 2 gene polymorphism and advanced glycation end products as risk factors for diabetic nephropathy.

Hepatocellular carcinoma (HCC) is a multifactorial disease with both genetic and environmental factors contributing to its pathogenesis. ACYP2 is a gene that is related to cell differentiation, apoptosis and prevention of malignant tumors. The ACYP2 gene also affects telomere length. The aim of this study was to evaluate the association between ACYP2 single nucleotide polymorphisms (SNPs) (rs843711), and (rs843706) and incidence of HCC in Egyptian HCC patients. The study included 30 patients with HCC and 30 normal controls. Detection of ACYP2 gene SNPs rs843711, and rs843706 in all study participants was done using real time polymerase chain reaction (RT-PCR). The results showed that all participants including HCC patients and controls carried the heterozygous CA (100%) of the rs843706 SNP (p> 0.05). As for the rs843711, 3.3% of HCC patients had the homozygous TT genotype, 46.7% had the heterozygous CT genotype and 50% had the wild CC genotype, while in the control group, 60% had the heterozygous CT genotype and 40% had the wild CC genotype with no significant difference between both groups (p>0.05). We concluded that there was no association between SNPs ACYP2 rs843706 and rs843711 and occurrence of HCC.

Ginger and its constituents in asthma: a mini-review.

OBJECTIVE: The primary objective of this review is to focus on research findings that aim to determine the immunomodulatory action of ginger's active components and the molecular mechanisms that reduce asthma. The study aims to provide an overview of the scientific literature available on ginger's efficacy in treating allergic asthma. DATA SOURCE: The mouse model of asthma has been used to investigate the actions of ginger and its active compounds on allergies and asthma. Various studies and scientific literature on ginger's health-improving qualities and its traditional use have been examined. RESULTS: The findings indicate that ginger and its active ingredients have anti-asthmatic features and a suppressive impact on mast cell production of histamine. Animals given ginger and compounds derived from ginger demonstrate a notable reduction in allergic response, suggesting a significant role in lowering the allergic reaction. CONCLUSION: While ginger shows promise as a potential treatment for allergies and asthma due to its anti-inflammatory, antibacterial, antidiabetic, anticancer, and antioxidant effects, further examination, extrapolation, and confirmation of these results are necessary before utilizing ginger and its active components in human treatments. This review highlights the need for additional research and provides an overview of the current scientific literature on ginger's efficacy in treating allergic asthma.

Characteristics and Outcomes of Stem Cell Transplant Patients during the COVID-19 Era: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to identify the outcomes of stem cell transplant (SCT) patients during the COVID-19 era. Pooled event rates (PER) were calculated, and meta-regression was performed. A random effects model was utilized. In total, 36 eligible studies were included out of 290. The PER of COVID-19-related deaths and COVID-19-related hospital admissions were 21.1% and 55.2%, respectively. The PER of the use of hydroxychloroquine was 53.27%, of the receipt of immunosuppression it was 39.4%, and of the use of antivirals, antibiotics, and steroids it was 71.61%, 37.94%, and 18.46%, respectively. The PER of the time elapsed until COVID-19 infection after SCT of more than 6 months was 85.3%. The PER of fever, respiratory symptoms, and gastrointestinal symptoms were 70.9, 76.1, and 19.3%, respectively. The PER of acute and chronic GvHD were 40.2% and 60.9%, respectively. SCT patients are at a higher risk of severe COVID-19 infection and mortality. The use of dexamethasone improves the survival of hospitalized SCT patients with moderate to severe COVID-19 requiring supplemental oxygen or ventilation. The SCT patient group is a heterogeneous group with varying characteristics. The quality of reporting on these patients when infected with COVID-19 is not uniform and further prospective or registry studies are needed to better guide clinical care in this unique setting.

Docosahexaenoic Acid Counteracts the Hypoxic-Induced Inflammatory and Metabolic Alterations in 3T3-L1 Adipocytes.

BACKGROUND: Hypoxia is caused by the excessive expansion of the white adipose tissue (AT) and is associated with obesity-related conditions such as insulin resistance, inflammation, and oxidative stress. Docosahexaenoic acid (DHA) is an omega-3 fatty acid reported to have beneficial health effects. However, the effects of DHA in AT against hypoxia-induced immune-metabolic perturbations in adipocytes exposed to low O2 tension are not well known. Consequently, this study aimed to evaluate the impact of DHA on markers of inflammation, metabolism, apoptosis, and oxidative stress in 3T3-L1 cell adipocytes exposed to low O2 tension (1% O2) induced hypoxia. METHODS: The apoptosis and reactive oxygen species (ROS) rates were evaluated. Metabolic parameters such as lactate, FFA, glycerol release, glucose uptake, and ATP content were assessed by a fluorometer. The expression of HIF-1, GLUT1 and the secretion of adipocytokines such as leptin, adiponectin, and pro-inflammatory markers was evaluated. RESULTS: DHA-treated hypoxic cells showed significantly decreased basal free fatty acid release, lactate production, and enhanced glucose consumption. In addition, DHA-treatment of hypoxic cells caused a significant reduction in the apoptosis rate and ROS production with decreased lipid peroxidation. Moreover, DHA-treatment of hypoxic cells caused a decreased secretion of pro-inflammatory markers (IL-6, MCP-1) and leptin and increased adiponectin secretion compared with hypoxic cells. Furthermore, DHA-treatment of hypoxic cells caused significant reductions in the expression of genes related to hypoxia (HIF-1, HIF-2), anaerobic metabolism (GLUT1 and Ldha), ATP production (ANT2), and fat metabolism (FASN and PPARY). CONCLUSION: This study suggests that DHA can exert potential anti-obesity effects by reducing the secretion of inflammatory adipokines, oxidative stress, lipolysis, and apoptosis.

Diabetes Self-Management and Health-Related Quality of Life among Primary Care Patients with Diabetes in Qatar: A Cross-Sectional Study.

Diabetes self-management (DSM) practices are an important determinant of health-related outcomes, including health-related quality of life (HRQOL). The purpose of this study is to explore DSM practices and their relationship with the HRQOL of patients with type 2 diabetes in primary health care centers (PHCCs) in Qatar. In this cross-sectional study, data were collected from PHCC patients with diabetes via interview-administered questionnaires by utilizing two instruments: the DSM questionnaire (DSMQ) and the HRQOL Short Form (SF-12). Frequencies were calculated for categorical variables and medians were calculated for continuous variables that were not normally distributed. A statistical comparison between groups was conducted using chi-square for categorical data. Binary logistic regression was utilized to examine the relationship between the significant independent factors and the dependent variables. A total of 105 patients completed the questionnaire, 51.4% of whom were male. Approximately half of the participants (48.6%) reported poor overall DSM practices, and 50.5% reported poor physical health quality of life (PC) and mental health quality of life (MC). Female participants showed significantly higher odds of reporting poor DSM than male participants (OR, 4.77; 95% CI, 1.92-11.86; p = 0.001). Participants with a secondary education (OR, 0.18; 95% CI, 0.04-0.81; p = 0.025) and university education (OR, 0.18; 95% CI, 0.04-0.84; p = 0.029) showed significantly lower odds of reporting poor DSM than participants with no/primary education. Older participants showed higher odds of reporting poor PC than younger participants (OR 11.04, 95% CI, 1.47-82.76 and OR 8.32; 95% CI, 1.10-62.86, respectively). Females also had higher odds for poor PC than males (OR 7.08; 95% CI, 2.21-22.67), while participants with a secondary (OR, 0.13; 95% CI, 0.03-0.62; p = 0.010) and university education (OR, 0.11; 95% CI, 0.02-0.57; p = 0.008) showed significantly lower odds of reporting poor MC. In conclusion, patients with diabetes reported poor overall DSM practices and poor HRQOL. Our findings suggest intensifying efforts to deliver culturally appropriate DSM education to patients and to empower patients to take charge of their health.

Lab-scale Preparation of Recombinant Human Insulin-like Growth Factor-1 in Escherichia coli and its Potential Safety on Normal Human Lung Cell Line.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is structurally similar to insulin and acts as an endocrine hormone secreted by the liver. OBJECTIVE: Production of recombinant human IGF-1 (rhIGF-1) in Escherichia coli (E.coli) and evaluation of its proliferation stimulatory activity. METHODS: hIGF-1 gene cloned into pBSK (+) simple vector was transformed into TOP 10 chemically competent cells of E. coli. Polymerase chain reaction (PCR) was achieved using specific hIGF-1 gene primers to confirm the successful transformation. To express the rhIGF-1 in E. coli (Rosetta (DE3) pLysS); the hIGF-1 gene was cloned into the pET-15b expression vector and then the recombinant pET-15b/IGF-1 vector was transformed into a chemically prepared competent expression bacterial cells; Rosetta (DE3) pLysS. The rhIGF-1 was expressed as insoluble aggregates called inclusion bodies (IBs) using a 2 mM Isopropyl ß-D-1-thiogalactopyranoside (IPTG) inducer. IBs were solubilized in a denatured form using 6 M guanidinium hydrochloride (GdmCl), followed by in vitro protein refolding using the rapid dilution method. The refolded hIGF-1 was purified using the HiTrap- ANX anion exchange column. Western blot and ELISA using rabbit polyvalent anti-hIGF- 1 were performed to confirm the protein antigenic identity. Cell proliferation activity of rhIGF-1 was testified on normal human lung cell line (WI-38). RESULTS: rhIGF-1 was purified from the HiTrap-ANX column at a concentration of 300 µg/ml. Western blot showed a single 7.6 kDa band obtained in the induced Rosetta (DE3) pLYsS. ELISA confirmed the molecular identity of the rhIGF-1 epitope, the concentration of purified rhIGF-1 obtained from the ELISA standard curve using rhIGF-1 reference protein as a standard was 300 µg/ml, and activity on WI-38 cells was 2604.17I U/mg. CONCLUSION: Biologically active native rhIGF-1 protein was successfully expressed. Patents related to the preparation of IGF-1 were mentioned along the text.

Sulforaphane reduces obesity by reversing leptin resistance.

The ascending prevalence of obesity in recent decades is commonly associated with soaring morbidity and mortality rates, resulting in increased health-care costs and decreased quality of life. A systemic state of stress characterized by low-grade inflammation and pathological formation of reactive oxygen species (ROS) usually manifests in obesity. The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) is the master regulator of the redox homeostasis and plays a critical role in the resolution of inflammation. Here, we show that the natural isothiocyanate and potent NRF2 activator sulforaphane reverses diet-induced obesity through a predominantly, but not exclusively, NRF2-dependent mechanism that requires a functional leptin receptor signaling and hyperleptinemia. Sulforaphane does not reduce the body weight or food intake of lean mice but induces an anorectic response when coadministered with exogenous leptin. Leptin-deficient Lepob/ob mice and leptin receptor mutant Leprdb/db mice display resistance to the weight-reducing effect of sulforaphane, supporting the conclusion that the antiobesity effect of sulforaphane requires functional leptin receptor signaling. Furthermore, our results suggest the skeletal muscle as the most notable site of action of sulforaphane whose peripheral NRF2 action signals to alleviate leptin resistance. Transcriptional profiling of six major metabolically relevant tissues highlights that sulforaphane suppresses fatty acid synthesis while promoting ribosome biogenesis, reducing ROS accumulation, and resolving inflammation, therefore representing a unique transcriptional program that leads to protection from obesity. Our findings argue for clinical evaluation of sulforaphane for weight loss and obesity-associated metabolic disorders.

In vitro and in vivo evaluation of taste-masked orodispersible tablets of fluoxetine hydrochloride for the treatment of depression.

AIM: Fluoxetine (FLX) has become the first-line drug in the pharmacotherapy of patients with depression. However, it has a strong unpleasant bitter taste, leading to the failure to complete the therapy. In this study, FLX is formulated into orodispersible tablets (ODTs) characterized by a fast release with an acceptable taste. METHOD: FLX ODTs were prepared by the complexation of FLX with ß-cyclodextrin (ß-CD) for taste-masking, using different super disintegrants, namely crospovidone (CP), croscarmellose sodium (Ccs), sodium starch glycolate (SSG), and indion. The FLX powder blend is estimated for pre-and post-compression parameters. The selected tablet formulations based upon drug release at 40 s with acceptable release patterns are investigated for accelerated stability testing and comparative in vivo study with a marketed product. RESULTS: It was found that all FLX-powder blends have good flow properties; all the prepared tablets complied with the pharmacopeial requirements for the unity of content, weight, friability, and hardness. Moreover, all the tablets obtained acceptable taste after complexation with ß-CD. The order of release of the drug, regarding super disintegrants used, was as in the following descending order: CP > Ccs > SSG > indion. Accelerated stability study of selected formulation F2 and F6 showed that; there were no considerable changes in physical properties, drug content, and percentage drug release. Furthermore, also the in vivo study proved the effectiveness of FLX ODTs as an antidepressant. CONCLUSION: The results obtained showed a promising potential of the prepared FLX ODTs for treating depression effectively.

Fabrication of titanium dioxide nanomaterial for implantable highly flexible composite bioelectrode for biosensing applications.

Implantable and stretchable electrodes have managed to progress the medical field from a medical diagnosis aspect to a patient treatment level. They offer the ability to detect biosignals and conduct electrical current to tissues that aid in muscle stimulation and axon regeneration. Current conventional electrodes are fabricated from stiff and very expensive, precious metals such as platinum. In this work, novel, low cost, and highly flexible electrode materials were fabricated based on titanium dioxide (TiO2) and polymethyl methacrylate (PMMA) supported by a silicone polymer matrix. The electrode materials were characterized by their electrochemical, mechanical, and surface properties. The electrodes possessed high flexibility with Young's modulus of 235 kPa, revealing highly stretchable characteristics. The impedance at 1 kHz was around 114.6 kΩ, and the charge capacity was 1.23 mC/cm2. The fabricated electrodes appeared to have a smooth surface, as seen in the scanning electron microscope micrographs, compared with electrodes in the literature. Long-time stability tests revealed an overall decrease in impedance and an increase in the charge capacity up to 475% of the initial value within three weeks.

Recent Advances in Metal-Organic Frameworks as Anticancer Drug Delivery Systems: A Review.

BACKGROUND: Metal-organic frameworks (MOFs), as attractive hybrid crystalline porous materials, are being increasingly investigated in biomedical applications owing to their exceptional properties, including high porosity, ultrahigh surface areas, tailorable composition and structure, and tunability and surface functionality. Of interest, in this review, is the design and development of MOF-based drug delivery systems (DDSs) that have excellent biocompatibility, good stability under physiological conditions, high drug loading capacity, and controlled/targeted drug release. OBJECTIVE: This review highlights the latest advances in MOFs as anticancer drug delivery systems (DDSs) along with insights on their design, fabrication, and performance under different stimuli that are either internal or external. The synthesis methods of MOFs, along with their advantages and disadvantages, are briefly discussed. The emergence of multifunctional MOF-based theranostic platforms is also discussed. Finally, the future challenges facing the developments of MOFs in the field of drug delivery are discussed. METHODS: The review was prepared by carrying out a comprehensive literature survey using relevant work published in various scientific databases. RESULTS: Novel MOFs in biomedical applications, especially in drug delivery, have shown great potential. MOF-based DDSs can be classified into normal (non-controllable) DDSs, stimuli-responsive DDSs, and theranostic platforms. The normal DDSs are pristine MOFs loaded with therapeutic agents and offer little to no control over drug release. Stimuli-responsive DDSs offer better spatiotemporal control over drug release by responding to either endogenous (pH, redox, ions, ATP) or exogenous stimuli (light, magnetism, US, pressure, temperature). The theranostic platforms combine stimuli-responsive drug delivery with diagnostic imaging functionality, paving the road for imaging-guided drug delivery. CONCLUSION: This review presented a summary of the various methods utilized in MOF's synthesis along with the advantages and disadvantages of each method. Furthermore, the review highlighted and discussed the latest developments in the field of MOF-based DDSs and theranostic platforms. The review is focused on the characteristics of MOF-based DDSs, the encapsulation of different anticancer drugs as well as their stimuli-responsive release.

Evaluation of scars in children after treatment with low-level laser.

Burn scars are known for their tendency to worsen with hypertrophy and contracture, causing esthetic and functional problems. The objective is to analyze the effectiveness of low-level laser therapy on post-burn hypertrophic scar tissue in children. A randomized controlled study included 15 children, ranging from 2 to 10 years of age, presented with post-burn hypertrophic scars. They received He-Ne laser and topical treatment. Each scar was divided into two halves. One half was treated with laser therapy and topical treatment (study area), and the other half was treated with topical treatment only (control area). The children were evaluated before, and after 3 months of the study by Vancouver Scar Scale (VSS), ultrasonography, and laser Doppler perfusion imaging. Significant improvement was reported in the studied area, compared to the control area for patients with P values (P = 0.003) and (P = 0.005), for VSS and U/S scores, respectively. No differences were detected for blood perfusion of the scar between both areas (P = 0.73). In addition, no adverse effects were reported. Photobiomodulation (PBM) is an efficient and safe therapeutic modality for post-burn hypertrophic scars in children, with no side effects, and should be considered a part of combination therapy for better results.

Photobiomodulation effect on children's scars.

The management of burn scars has become one of the major clinical challenges in the developing countries which involve enormous treatment cost; this needs new methods for better cost benefit relationship. The objective of the study is to analyze the effectiveness of low-level laser therapy on post-burn scar tissue in children. A randomized controlled study included 15 children, ranging from 2 to 10 years of age, presenting with burn scars. They received diode laser and topical treatment. Each scar was divided into two halves. One half was treated with laser therapy and topical treatment (study area), and the other half was treated with topical treatment only (control area). The children were evaluated before and after 3 months of the study by Vancouver Scar Scale (VSS), ultrasonography (U/S), and laser Doppler perfusion imaging. Significant improvement was reported in the studied area compared to the control area for patients with P values (P = 0.005) and (P = 0.0001) for VSS and U/S scores, respectively. No difference was detected for blood perfusion to the scar between both areas (P = 0.18). In addition, no adverse effect was reported. Photobiomodulation is an efficient and safe therapeutic modality for post-burn hypertrophic scars in children and should be considered a part of combination therapy for better results.

Ginger extract modulates Pb-induced hepatic oxidative stress and expression of antioxidant gene transcripts in rat liver.

CONTEXT: Spices and herbs are recognized sources of natural antioxidants that can protect from oxidative stress, thus play an important role in chemoprevention of liver diseases. Ginger is used worldwide primarily as a spicy condiment. OBJECTIVE: This study evaluated the ability of ginger extract (GE) to ameliorate oxidative-hepatic toxicity induced by lead acetate (PbAc) in rats. MATERIALS AND METHODS: Five groups of animals were used: group I kept as control; groups II, IV, and V received PbAc (1 ppm in drinking water daily for 6 weeks, and kept for an additional 2 weeks without PbAc exposure); group III treated orally with GE (350 mg/kg body weight, 4 d per week) for 6 weeks; group IV (protective) received GE for 2 weeks before and simultaneously with PbAc; and group V (treatment) received GE for 2 weeks after PbAc exposure. RESULTS: GC-MS analysis of GE revealed its content of gingerol (7.09%), quercetin (3.20%), dl-limonene (0.96%), and zingiberene (0.18%). Treatment of PbAc-treated rats with GE has no effect on hepatic Pb concentrations. However, it maintained serum aspartate aminotransferase level, increased hepatic glutathione (157%), glutathione S-transferase (GST) (228%), glutathione peroxidase (GPx) (138%) and catalase (CAT) (112%) levels, and reduced hepatic malondialdehyde (80%). Co-treatment of PbAc group with GE upregulated mRNA expression of antioxidant genes: GST-α1 (1.4-fold), GPx1 (1.8-fold), and CAT (8-fold), while post-treatment with GE upregulated only mRNA expression of GPx1 (1.5-fold). CONCLUSION: GE has an antioxidant protective efficacy against PbAc-induced hepatotoxicity, which appears more effective than its therapeutic application. However, the changes in antioxidant gene expression were not reflected at the protein level.

Using species-specific repeat and PCR-RFLP in typing of DNA derived from blood of human and animal species.

Species determination of tissue specimens, including blood, is an important component of forensic analysis to distinguish human from animal remains. DNA markers based on a method of species-specific PCR and amplifying the 359-base pair (bp) fragment of the mitochondrially encoded cytochrome-b gene and then digestion with the TaqI restriction enzyme were developed for detection and discrimination of human, cattle, buffalo, horse, sheep, pig, dog, cat and chicken blood samples. The results reveal that PCR-amplification of the gene encoding the species-specific repeat (SSR) region generated 603 bp in cattle and buffalo, 221 bp in horse, 374 bp in sheep,