Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma.

The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs can serve as oncogenes or tumor suppressors depending on the target genes. In MM, miRNA disruption could result in abnormal gene expression responsible for cell growth, apoptosis, and other biological processes pertinent to cancer development. The dysregulated miRNAs inhibit the activity of tumor suppressor genes, contributing to disease progression. Nonetheless, several miRNAs are downregulated in MM and have been identified as gene regulators implicated in extracellular matrix remodeling and cell adhesion. miRNA depletion potentially facilitates the tumor advancement and resistance of therapeutic drugs. Additionally, lncRNAs are key regulators of numerous cellular processes, such as gene expression, chromatin remodeling, protein trafficking, and recently linked MM development. The lncRNAs are uniquely expressed and influence gene expression that supports MM growth, in addition to facilitating cellular proliferation and viability via multiple molecular pathways. miRNA and lncRNA alterations potentially result in anomalous gene expression and interfere with the regular functioning of MM. Thus, this review aims to highlight the dysregulation of these ncRNAs, which engender novel therapeutic modalities for the treatment of MM.

Sustainable removal of phenol from wastewater using a biopolymer hydrogel adsorbent comprising crosslinked chitosan and κ-carrageenan.

A biopolymer-based adsorbent comprising chitosan (CS) and κ-carrageenan (κ-Carr) was synthesised and evaluated to treat phenolic-contaminated water. The developed CS/κ-Carr hydrogel demonstrated excellent performance with a phenol adsorption uptake of 80 %. The morphologies of CS/κ-Carr hydrogels with different ratios of CS to κ-Carr ranging from 1:2 to 7:3 were characterised using scanning electron microscopy and atomic force microscopy; their chemical structures were investigated by spectral analyses using Fourier-transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry; their adsorption characteristics were determined using tests for swelling, chemical stability, hygroscopic moisture content, and hydrophilicity. Finally, a batch-type evaluation method demonstrated adsorption performance at 25 °C and pH 6.9. Adsorption isotherms and kinetic data were successfully obtained using the Freundlich and pseudo-second-order models, respectively. The results indicate that one-pot synthesis of an insoluble CS/κ-Carr hydrogel adsorbent exhibits considerable potential for the removal of phenol from aqueous solutions, providing an environmentally friendly technology enhancing the phenol adsorption performance of CS.

A Compact and Low-Power SoC Design for Spiking Neural Network Based on Current Multiplier Charge Injector Synapse.

This paper presents a compact analog system-on-chip (SoC) implementation of a spiking neural network (SNN) for low-power Internet of Things (IoT) applications. The low-power implementation of an SNN SoC requires the optimization of not only the SNN model but also the architecture and circuit designs. In this work, the SNN has been constituted from the analog neuron and synaptic circuits, which are designed to optimize both the chip area and power consumption. The proposed synapse circuit is based on a current multiplier charge injector (CMCI) circuit, which can significantly reduce power consumption and chip area compared with the previous work while allowing for design scalability for higher resolutions. The proposed neuron circuit employs an asynchronous structure, which makes it highly sensitive to input synaptic currents and enables it to achieve higher energy efficiency. To compare the performance of the proposed SoC in its area and power consumption, we implemented a digital SoC for the same SNN model in FPGA. The proposed SNN chip, when trained using the MNIST dataset, achieves a classification accuracy of 96.56%. The presented SNN chip has been implemented using a 65 nm CMOS process for fabrication. The entire chip occupies 0.96 mm2 and consumes an average power of 530 µW, which is 200 times lower than its digital counterpart.

Effect of diet-induced weight loss on iron status and its markers among young women with overweight/obesity and iron deficiency anemia: a randomized controlled trial.

Introduction: Obesity and iron deficiency are prevalent health problems that affect billions of people all over the world. Obesity is postulated to relate to iron deficiency via reduced intestinal iron absorption due to increased serum hepcidin level, which is mediated by chronic inflammation. Weight loss in individuals with overweight or obesity and iron deficiency anemia is believed to be associated with an improvement in iron status however the evidence from clinical trials is scarce. This study was conducted to evaluate the effect of diet-induced weight loss on iron status and its markers among young women with overweight/obesity and iron deficiency anemia. Methods: The study design was a single-blinded, randomized controlled trial with two parallel arms (weight loss intervention vs control). Study participants were recruited using the convenience sampling method through public advertisements posted and disseminated through social media. Interested and potential participants were asked to visit the Diet Clinic for eligibility screening. A total of 62 women were recruited and randomized into weight loss intervention and control group. The intervention duration was three months. The intervention group received individual consultation sessions with the dietitian and tailored energy-restricted diets. Physical activity levels, dietary intake, anthropometric measurements and clinical markers were measured at baseline and end of the trial. Results: There was a significant decrease (p < 0.001) in body weight of the intervention group (-7.4 ± 2.7 kg) that was associated with significant improvements in iron status and its markers (p < 0.01). The intervention group experienced a significant increase in hemoglobin (0.5 ± 0.6 g/dL), serum ferritin (5.6 ± 5.8 ng/mL), and serum iron (13.0 ± 16.2 µg/dL), and a significant decrease in high-sensitivity C-reactive protein (-5.2 ± 5.6 mg/L), and serum hepcidin level (-1.9 ± 2.2 ng/mL) at the end of the trial. Conclusion: Our findings indicate that diet-induced weight loss among participants was associated with an improvement in iron status and its related clinical markers. Clinical Trial Registration: [https://www.thaiclinicaltrials.org/show/TCTR20221009001], identifier [TCTR20221009001].

Thymoquinone Enhances Apoptosis of K562 Chronic Myeloid Leukemia Cells through Hypomethylation of SHP-1 and Inhibition of JAK/STAT Signaling Pathway.

The epigenetic silencing of tumor suppressor genes (TSGs) is critical in the development of chronic myeloid leukemia (CML). SHP-1 functions as a TSG and negatively regulates JAK/STAT signaling. Enhancement of SHP-1 expression by demethylation provides molecular targets for the treatment of various cancers. Thymoquinone (TQ), a constituent of Nigella sativa seeds, has shown anti-cancer activities in various cancers. However, TQs effect on methylation is not fully clear. Therefore, the aim of this study is to assess TQs ability to enhance the expression of SHP-1 through modifying DNA methylation in K562 CML cells. The activities of TQ on cell cycle progression and apoptosis were evaluated using a fluorometric-red cell cycle assay and Annexin V-FITC/PI, respectively. The methylation status of SHP-1 was studied by pyrosequencing analysis. The expression of SHP-1, TET2, WT1, DNMT1, DNMT3A, and DNMT3B was determined using RT-qPCR. The protein phosphorylation of STAT3, STAT5, and JAK2 was assessed using Jess Western analysis. TQ significantly downregulated the DNMT1 gene, DNMT3A gene, and DNMT3B gene and upregulated the WT1 gene and TET2 gene. This led to hypomethylation and restoration of SHP-1 expression, resulting in inhibition of JAK/STAT signaling, induction of apoptosis, and cell cycle arrest. The observed findings imply that TQ promotes apoptosis and cell cycle arrest in CML cells by inhibiting JAK/STAT signaling via restoration of the expression of JAK/STAT-negative regulator genes.

HBB Gene Mutations and Their Pathological Impacts on HbE/ß-Thalassaemia in Kuala Terengganu, Malaysia.

BACKGROUND: ß-thalassaemia is a disorder caused by mutations in the ß-globin gene, leading to defective production of haemoglobins (Hb) and red blood cells (RBCs). It is characterised by anaemia, ineffective erythropoiesis, and iron overload. Patients with severe ß-thalassaemia require lifelong blood transfusions. Haemoglobin E beta-thalassaemia (HbE/ß-thalassaemia) is a severe form of ß-thalassaemia in Asian countries. More than 200 alleles have been recognised in the ß-globin region. Different geographical regions show different frequencies of allelic characteristics. In this study, the spectrum of ß-thalassaemia (ß-thal) alleles and their correlation with iron overload, in HbE/ß-thalassaemia patients, ß-thalassaemia trait, and HbE trait were studied. METHODS: Blood samples (n = 260) were collected from 65 ß-thalassaemia patients, 65 parents (fathers and/or mothers) and 130 healthy control individuals. Haematological analyses, iron profiles, and serum hepcidin levels were examined for all participants. DNA was extracted from patients' and their parents' blood samples, then subjected to PCR amplification. Multiplex amplification refractory mutation system PCR (MARMS-PCR) was conducted for eighteen primers to detect the mutations. RESULTS: There was severe anaemia present in HbE/ß-thalassaemia patients compared to their parents and healthy controls. The ferritin and iron levels were significantly increased in patients compared to their parents and healthy controls (p = 0.001). Two common mutations were detected among the patient group and three mutations were detected among their parents, in addition to seven novel mutations in HbE/ß-thalassaemia patients (explained in results). CONCLUSION: Some mutations were associated with severe anaemia in ß-thalassaemia patients. The detection of mutations is a prognostic marker, and could enhance the appropriate management protocols and improve the haematological and biochemical statuses of ß-thalassaemia patients.

Formulation and Characterization of Ethyl Cellulose-Based Patches Containing Curcumin-Chitosan Nanoparticles for the Possible Management of Inflammation via Skin Delivery.

Curcumin, a natural phenolic compound, exhibits poor absorption and extensive first pass metabolism after oral administration. In the present study, curcumin-chitosan nanoparticles (cur-cs-np) were prepared and incorporated into ethyl cellulose patches for the management of inflammation via skin delivery. Ionic gelation method was used for the preparation of nanoparticles. The prepared nanoparticles were evaluated for size, zetapotential, surface morphology, drug content, and % encapsulation efficiency. The nanoparticles were then incorporated into ethyl cellulose-based patches using solvent evaporation technique. ATR-FTIR was used to study/assess incompatibility between drug and excipients. The prepared patches were evaluated physiochemically. The in vitro release, ex vivo permeation, and skin drug retention studies were carried out using Franz diffusion cells and rat skin as permeable membrane. The prepared nanoparticles were spherical, with particle size in the range of 203-229 nm, zetapotential 25-36 mV, and PDI 0.27-0.29 Mw/Mn. The drug content and %EE were 53% and 59%. Nanoparticles incorporated patches are smooth, flexible, and homogenous. The in vitro release and ex vivo permeation of curcumin from nanoparticles were higher than the patches, whereas the skin retention of curcumin was significantly higher in case of patches. The developed patches deliver cur-cs-np into the skin, where nanoparticles interact with skin negative charges and hence result in higher and prolonged retention in the skin. The higher concentration of drug in the skin helps in better management of inflammation. This was shown by anti-inflammatory activity. The inflammation (volume of paw) was significantly reduced when using patches as compared to nanoparticles. It was concluded that the incorporation of cur-cs-np into ethyl cellulose-based patches results in controlled release and hence enhanced anti-inflammatory activity.

Transformation of hazardous sacred incense sticks ash waste into less toxic product by sequential approach prior to their disposal into the water bodies.

Incense sticks ash is one of the most unexplored by-products generated at religious places and houses obtained after the combustion of incense sticks. Every year, tonnes of incense sticks ash is produced at religious places in India which are disposed of into the rivers and water bodies. The presence of heavy metals and high content of alkali metals challenges a potential threat to the living organism after the disposal in the river. The leaching of heavy metals and alkali metals may lead to water pollution. Besides this, incense sticks also have a high amount of calcium, silica, alumina, and ferrous along with traces of rutile and other oxides either in crystalline or amorphous phases. The incense sticks ash, heavy metals, and alkali metals can be extracted by water, mineral acids, and alkali. Ferrous can be extracted by magnetic separation, while calcium by HCl, alumina by sulfuric acid treatment, and silica by strong hydroxides like NaOH. The recovery of such elements by using acids and bases will eliminate their toxic heavy metals at the same time recovering major value-added minerals from it. Here, in the present research work, the effect on the elemental composition, morphology, crystallinity, and size of incense sticks ash particles was observed by extracting ferrous, followed by extraction of calcium by HCl and alumina by H2SO4 at 90-95 °C for 90 min. The final residue was treated with 4 M NaOH, in order to extract leachable silica at 90 °C for 90 min along with continuous stirring. The transformation of various minerals phases and microstructures of incense sticks ash (ISA) and other residues during ferrous, extraction, calcium, and alumina and silica extraction was studied using Fourier transform infrared (FTIR), dynamic light scattering (DLS), X-ray fluorescence (XRF), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and inductively coupled plasma-optical emission spectroscopy (ICP-OES). DLS was used for analyzing the size during the experiments while FTIR helped in the confirmation of the formation of new products during the treatments. From the various instrumental analyses, it was found that the toxic metals present in the initial incense sticks ash got eliminated. Besides this, the major alkali metals, i.e., Ca and Mg, got reduced during these successive treatments. Initially, there were mainly irregular shaped, micron-sized particles that were dominant in the incense sticks ash particles. Besides this, there were plenty of carbon particles left unburned during combustion. In the final residue, nanosized flowers shaped along with cuboidal micron-sized particles were dominant. present in If, such sequential techniques will be applied by the industries based on recycling of incense sticks ash, then not only the solid waste pollution will be reduced but also numerous value-added minerals like ferrous, silica, alumina calcium oxides and carbonates can be recovered from such waste. The value-added minerals could act as an economical and sustainable source of adsorbent for wastewater treatment in future.

Graphene Oxide-Polyphenylsulfone Nanocomposite Beads for Paracetamol Removal from Aqueous Solution.

This study introduces a promising and practical method for the removal of paracetamol from aqueous environments, employing graphene oxide-polymer nanocomposite beads. The approach involves the utilization of a straightforward and facile phase inversion method, offering a convenient and efficient one-step process for the creation of adsorbent beads by integrating polymers and graphene oxide (GO). The synthesized nanocomposite beads are tailored for the removal of paracetamol from simulated wastewater in batch systems. Extensive characterization techniques including XPS, FTIR, SEM, TGA, and zeta potential analysis are employed to scrutinize the chemical properties and structural attributes of the prepared beads. The investigation explores the impact of critical parameters such as adsorbent dosage, adsorption duration, initial paracetamol concentration, and solution pH on the adsorption process. These nanocomposite beads exhibit an exceptional paracetamol removal efficiency, achieving up to 99% removal. This research not only contributes to the advancement of efficient and sustainable adsorbent materials for pollutant removal but also underscores their potential for environmentally friendly and cost-effective solutions in the domain of wastewater treatment.

The Wheat Head Blight Pathogen Fusarium graminearum Can Recruit Collaborating Bacteria from Soil.

In nature, fungal endophytes often have facultative endohyphal bacteria (FEB). Can a model plant pathogenic fungus have them, and does it affect their phenotype? We constructed a growth system/microcosm to allow an F. graminearum isolate to grow through natural soil and then re-isolated it on a gentamicin-containing medium, allowing endohyphal growth of bacteria while killing other bacteria. F. graminearum PH-1 labelled with a His1mCherry gene staining the fungal nuclei fluorescent red was used to confirm the re-isolation of the fungus. Most new re-isolates contained about 10 16SrRNA genes per fungal mCherry gene determined by qPCR. The F. graminearum + FEB holobiont isolates containing the bacteria were sub-cultured several times, and their bacterial contents were stable. Sequencing the bacterial 16SrRNA gene from several Fg-FEB holobiont isolates revealed endophytic bacteria known to be capable of nitrogen fixation. We tested the pathogenicity of one common Fg-FEB holobiont association, F. graminearum + Stenatrophomonas maltophilia, and found increased pathogenicity. The 16SrRNA gene load per fungal His1mCherry gene inside the wheat stayed the same as previously found in vitro. Finally, strong evidence was found for Fg-S. maltophilia symbiotic nitrogen fixation benefitting the fungus.

Thymoquinone Inhibits JAK/STAT and PI3K/Akt/ mTOR Signaling Pathways in MV4-11 and K562 Myeloid Leukemia Cells.

Constitutive activation of Janus tyrosine kinase-signal transducer and activator of transcription (JAK/STAT) and Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways plays a crucial role in the development of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Thymoquinone (TQ), one of the main constituents of Nigella sativa, has shown anti-cancer activities in several cancers. However, the inhibitory effect mechanism of TQ on leukemia has not been fully understood. Therefore, this study aimed to investigate the effect of TQ on JAK/STAT and PI3K/Akt/mTOR pathways in MV4-11 AML cells and K562 CML cells. FLT3-ITD positive MV4-11 cells and BCR-ABL positive K562 cells were treated with TQ. Cytotoxicity assay was assessed using WSTs-8 kit. The expression of the target genes was evaluated using RT-qPCR. The phosphorylation status and the levels of proteins involved in JAK/STAT and PI3K/Akt/mTOR pathways were investigated using Jess western analysis. TQ induced a dose and time dependent inhibition of K562 cells proliferation. TQ significantly downregulated PI3K, Akt, and mTOR and upregulated PTEN expression with a significant inhibition of JAK/STAT and PI3K/Akt/mTOR signaling. In conclusion, TQ reduces the expression of PI3K, Akt, and mTOR genes and enhances the expression of PTEN gene at the mRNA and protein levels. TQ also inhibits JAK/STAT and PI3K/Akt/mTOR pathways, and consequently inhibits proliferation of myeloid leukemia cells, suggesting that TQ has potential anti-leukemic effects on both AML and CML cells.

Adductor canal block versus femoral nerve block for pain control after total knee arthroplasty: A systematic review and Meta-analysis.

BACKGROUND: Femoral nerve block is a widely accepted nerve block method with evident reduction in consumption of opioid painkiller and minimization of the duration of hospital stay but may cause weakness of quadriceps muscle strength. Adductor canal block is another nerve block technique that attracts the attention of scientific community nowadays because of its possible superiority over Femoral nerve block regarding mobility and muscle strength. METHODS: This is a systematic review and meta-analysis of 33 studies, aiming to compare femoral nerve block with adductor canal block following total knee arthroplasty regarding pain control and mobilization. RESULTS: Adductor canal block showed better preservation of quadriceps muscle strength (MD = 0.28, 95% CI [0.11, 0.46], P = .002), and better mobilization up to 2 days postoperatively. However, no significant difference was found between the 2 interventions regarding pain control (MD = 0.06, 95% CI [-0.06, 0.17], P = .33) or opioid consumption (SMD = 0.08, 95% CI [-0.06, 0.22], P = .28) up to 2 days postoperatively. The better mobilization results of adductor canal block did not translate into a significant difference in the risk of falls or patients' satisfaction; however, adductor canal block patients had less mean length of hospital stay than the patients with femoral nerve block. CONCLUSION: Both femoral nerve block and adductor canal block provide similar results regarding pain control and opioid consumption, however adductor canal block provides better preservation of quadriceps strength and mobilization, giving it more advantage over femoral nerve block.

Meriandra dianthera Aqueous Extract and Its Fraction Prevents Blood Coagulation by Specifically Inhibiting the Intrinsic Coagulation Pathway: An in vitro Study.

Background: Currently, cardiovascular disorders are the primary cause of mortality in the world and constitute a serious medical problem. Blood coagulation is an essential process to prevent excessive blood loss through injured blood vessels; however, abnormal blood clotting in the blood vessels can result in fatal cardiovascular disorders. This study investigated the in vitro anticoagulant activity of Meriandra dianthera crude extract and its fractions and their erythrocyte membrane stabilizing activity. Methods: The plant leaves were extracted by a decoction method and were further fractionated by a liquid-liquid partition with a solvent of crescent polarity. The in vitro anticoagulant activity of the plant extract and its fractions was assessed by PT and APTT assays, while the membrane stabilizing activity was determined through hypotonic induced hemolysis. Results: The crude aqueous leaf extract of Meriandra dianthera significantly (P < 0.001) prolonged the intrinsic clotting pathway measured by APTT by specifically acting on the intrinsic coagulation pathway. By using liquid-liquid fractionation, the residual aqueous fraction was identified as the fraction responsible for the anticoagulant activity of the crude extract as it significantly (P<0.001) prolonged APTT while the other fractions failed. Both the crude extract and its aqueous residue fraction did not affect the extrinsic coagulation pathway measured by PT. In the membrane stabilizing assay, crude extract and aqueous residue fraction showed the highest membrane stabilizing activity. Conclusion: The crude extract and its aqueous residue fraction showed a potent in vitro anticoagulant and membrane stabilizing activity, which shows the potential of the plant's leaves as a new source of bioactive molecules for coagulation-related disorders.

Potential Mechanisms of Transmission of Tick-Borne Viruses at the Virus-Tick Interface.

Ticks (Acari; Ixodidae) are the second most important vector for transmission of pathogens to humans, livestock, and wildlife. Ticks as vectors for viruses have been reported many times over the last 100 years. Tick-borne viruses (TBVs) belong to two orders (Bunyavirales and Mononegavirales) containing nine families (Bunyaviridae, Rhabdoviridae, Asfarviridae, Orthomyxovirida, Reoviridae, Flaviviridae, Phenuviridae, Nyamiviridae, and Nairoviridae). Among these TBVs, some are very pathogenic, causing huge mortality, and hence, deserve to be covered under the umbrella of one health. About 38 viral species are being transmitted by <10% of the tick species of the families Ixodidae and Argasidae. All TBVs are RNA viruses except for the African swine fever virus from the family Asfarviridae. Tick-borne viral diseases have also been classified as an emerging threat to public health and animals, especially in resource-poor communities of the developing world. Tick-host interaction plays an important role in the successful transmission of pathogens. The ticks' salivary glands are the main cellular machinery involved in the uptake, settlement, and multiplication of viruses, which are required for successful transmission into the final host. Furthermore, tick saliva also participates as an augmenting tool during the physiological process of transmission. Tick saliva is an important key element in the successful transmission of pathogens and contains different antimicrobial proteins, e.g., defensin, serine, proteases, and cement protein, which are key players in tick-virus interaction. While tick-virus interaction is a crucial factor in the propagation of tick-borne viral diseases, other factors (physiological, immunological, and gut flora) are also involved. Some immunological factors, e.g., toll-like receptors, scavenger receptors, Janus-kinase (JAK-STAT) pathway, and immunodeficiency (IMD) pathway are involved in tick-virus interaction by helping in virus assembly and acting to increase transmission. Ticks also harbor some endogenous viruses as internal microbial faunas, which also play a significant role in tick-virus interaction. Studies focusing on tick saliva and its role in pathogen transmission, tick feeding, and control of ticks using functional genomics all point toward solutions to this emerging threat. Information regarding tick-virus interaction is somewhat lacking; however, this information is necessary for a complete understanding of transmission TBVs and their persistence in nature. This review encompasses insight into the ecology and vectorial capacity of tick vectors, as well as our current understanding of the predisposing, enabling, precipitating, and reinforcing factors that influence TBV epidemics. The review explores the cellular, biochemical, and immunological tools which ensure and augment successful evading of the ticks' defense systems and transmission of the viruses to the final hosts at the virus-vector interface. The role of functional genomics, proteomics, and metabolomics in profiling tick-virus interaction is also discussed. This review is an initial attempt to comprehensively elaborate on the epidemiological determinants of TBVs with a focus on intra-vector physiological processes involved in the successful execution of the docking, uptake, settlement, replication, and transmission processes of arboviruses. This adds valuable data to the existing bank of knowledge for global stakeholders, policymakers, and the scientific community working to devise appropriate strategies to control ticks and TBVs.

Problems faced by patients and health service utilization experiences of gastrointestinal patients during lockdown due to COVID-19 pandemic.

Objectives: The COVID-19 pandemic undermined the health service delivery and utilization of essential health care services globally. The current study therefore aimed to explore the health-seeking behaviors and challenges faced by patients for the management of gastrointestinal diseases. Methods: A cross-sectional study was conducted at the outpatient department of Gastroenterology, Liaquat National Hospital, Karachi from March 2020 to July 2020 during the COVID-19 lockdown phase to explore patient experiences. Data was collected using a survey questionnaire. All patients of either gender were included after informed consent. Statistical analysis of the data was conducted using SPSS 21.0. Results: A total of 184 patients were included who visited the hospital to seek medical services during the COVID-19 lockdown phase. The mean age of the population was 42.7 years (±16.13). Of these, n=94 (51.1%) were males All patients had gastrointestinal issues with different comorbid conditions. One forty-seven n=147 (79.9%) presented with active complaints whereas, n=37 (20.1%) patients visited the hospital for their follow-up checkup. Out of 184 patients, n=33 (17.9%) patients reported of having fear of visiting hospital due to COVID-19 outbreak. A statistically significant difference p<0.001 was noted between the history of comorbidities and patient delaying a visit to the healthcare due to the fear of COVID-19. Additionally, 61 (73.5%) patients with co-morbidity faced difficulty in finding public transport (p=0.01). Nevertheless, n=171 (93.0%) patients expressed satisfaction with the services provided by the hospital during the lockdown phase. Conclusion: Patients with gastrointestinal conditions were largely affected by lockdown largely due to fear of contacting COVID-19 disease and inaccessibility to the public transportation. Widely available telemedicine service might overcome these shortcomings and ensure continuity of quality care.

Characterization, in-silico, and in-vitro study of a new steroid derivative from Ophiocoma dentata as a potential treatment for COVID-19.

The medicinal potential of marine invertebrates' bioactive components that may act as anti-COVID-19 demonstrated promising results. Ophiocoma dentata, which is common in the Red Sea, is one such source. Therefore, this study aimed to isolate a new compound from the brittle star, Ophiocoma dentata, and evaluate its efficacy as anti-COVID-19 in-silico and in-vitro. Standard procedures were followed in order to assess the isolated compound's preliminary toxicity and anti-inflammatory properties. Computer virtual screening technology through molecular docking and ADMET studies was conducted as well as a new steroid derivative was isolated for the first time, named 5α-cholesta-4(27), 24-dien-3ß, 23 ß-diol. Investigation of the Anti-Covid-19 activity of the isolated compound using a Plaque reduction assay revealed 95% inhibition at a concentration of 5 ng/µl (12.48 µM). Moreover, this compound showed an IC50 of 11,350 ± 1500 ng/ml against the normal fibroblast cells, indicating its safety. Interestingly, this compound exhibited anti-inflammatory activity with an IC50 of 51.92 ± 0.03 µg/ml compared to a reference drug's IC50 of 53.64 ± 0.01 µg/ml, indicating that this compound is a potent anti-inflammatory. In silico data have proved that the isolated compound is a promising viral inhibitor against SARS-CoV2 and is thus recommended as a future nature preventive and curative antiviral drug.

Gene Expression Profiling and Protein Analysis Reveal Suppression of the C-Myc Oncogene and Inhibition JAK/STAT and PI3K/AKT/mTOR Signaling by Thymoquinone in Acute Myeloid Leukemia Cells.

Overexpression of c-Myc plays an essential role in leukemogenesis and drug resistance, making c-Myc an attractive target for cancer therapy. However, targeting c-Myc directly is impossible, and c-Myc upstream regulator pathways could be targeted instead. This study investigated the effects of thymoquinone (TQ), a bioactive constituent in Nigella sativa, on the activation of upstream regulators of c-Myc: the JAK/STAT and PI3K/AKT/mTOR pathways in HL60 leukemia cells. Next-generation sequencing (NGS) was performed for gene expression profiling after TQ treatment. The expression of c-Myc and genes involved in JAK/STAT and PI3K/AKT/mTOR were validated by quantitative reverse transcription PCR (RT-qPCR). In addition, Jess assay analysis was performed to determine TQ's effects on JAK/STAT and PI3K/AKT signaling and c-Myc protein expression. The results showed 114 significant differentially expressed genes after TQ treatment (p < 0.002). DAVID analysis revealed that most of these genes' effect was on apoptosis and proliferation. There was downregulation of c-Myc, PI3K, AKT, mTOR, JAK2, STAT3, STAT5a, and STAT5b. Protein analysis showed that TQ also inhibited JAK/STAT and PI3K/AKT signaling, resulting in inhibition of c-Myc protein expression. In conclusion, the findings suggest that TQ potentially inhibits proliferation and induces apoptosis in HL60 leukemia cells by downregulation of c-Myc expression through inhibition of the JAK/STAT and PI3K/AKT signaling pathways.

Modeling predictive suitability to identify the potential of wind and solar energy as a driver of sustainable development in the Red Sea state, Sudan.

This paper investigated the potential and economic validity of wind and solar energy at 17 selected locations in the Red Sea state, Sudan, for the first time. To this aim, the NASA database was utilized. The results demonstrated that vertical axis wind turbines would be a good solution for electricity generation for building in the selected locations. Additionally, it is found that the chosen areas are suitable for installing photovoltaic (PV) systems due to the high-value solar radiation. Moreover, the economic viability of small-scale wind and PV systems for rooftop buildings in the selected regions is investigated. For a financial analysis of wind turbines, the performance of different characteristics of vertical axis winds was evaluated based on the determination of capacity factor and energy production cost. For the economic validity of installing PV systems, RETScreen Expert software was used. The results indicate that the annual production energy from wind turbines and solar power is within the range of 158.50-29,063.93kWh and 6648-15,533 kWh, respectively. This amount of energy output would reduce the effect of global warming and enhance the sustainable technological development of the country. Moreover, the results indicate that model#9 (Vertical Axis Wind Generator-V) with a capacity of 5 kW has the lowest cost value (0.08703-0.01025 $/kWh) compared to the other selected turbines for the studied locations. Besides, the average energy production cost is within the range of 0.036-0.049 $/kWh for PV systems. In the end, it is concluded that using small-scale renewable energy systems will help reduce the electricity bills and the dependency on fossil fuels, the effect of global warming, and enhance the country's sustainable technological development.

Activation of STAT and SMAD Signaling Induces Hepcidin Re-Expression as a Therapeutic Target for ß-Thalassemia Patients.

Iron homeostasis is regulated by hepcidin, a hepatic hormone that controls dietary iron absorption and plasma iron concentration. Hepcidin binds to the only known iron export protein, ferroportin (FPN), which regulates its expression. The major factors that implicate hepcidin regulation include iron stores, hypoxia, inflammation, and erythropoiesis. When erythropoietic activity is suppressed, hepcidin expression is hampered, leading to deficiency, thus causing an iron overload in iron-loading anemia, such as ß-thalassemia. Iron overload is the principal cause of mortality and morbidity in ß-thalassemia patients with or without blood transfusion dependence. In the case of thalassemia major, the primary cause of iron overload is blood transfusion. In contrast, iron overload is attributed to hepcidin deficiency and hyperabsorption of dietary iron in non-transfusion thalassemia. Beta-thalassemia patients showed marked hepcidin suppression, anemia, iron overload, and ineffective erythropoiesis (IE). Recent molecular research has prompted the discovery of new diagnostic markers and therapeutic targets for several diseases, including ß-thalassemia. In this review, signal transducers and activators of transcription (STAT) and SMAD (structurally similar to the small mothers against decapentaplegic in Drosophila) pathways and their effects on hepcidin expression have been discussed as a therapeutic target for ß-thalassemia patients. Therefore, re-expression of hepcidin could be a therapeutic target in the management of thalassemia patients. Data from 65 relevant published experimental articles on hepcidin and ß-thalassemia between January 2016 and May 2021 were retrieved by using PubMed and Google Scholar search engines. Published articles in any language other than English, review articles, books, or book chapters were excluded.