Vaccines for Covid-19: An insight on their effectiveness and adverse effects.

An era of SARS-COVID-19 outbreak with a high contagious percentage around the globe has been the subject of multi-agency research aimed at generating vaccines for active immunization. Scientists across the world are joining hands for advanced tie-ups between medical start-ups and pharmaceutical industries for devices and vaccines development to hinder the progress of this outbreak. Moreover, the questions that need to be answered are how to improve the effectiveness and efficacy of vaccines with reduced side effects and the required doses of vaccines for enhanced surveillance. In this review article, we have discussed the effectiveness and efficacy of different Covid-19 vaccines.

Synthesis of [1-8-NαC]-zanriorb A1, alanine-containing analogues, and their cytotoxic and anti-inflammatory activity.

The synthesis of the orbitide[1-8-NαC]-zanriorb A1, isolated from the medicinal plant Zanthoxylum riedelianum, was investigated by solution-phase macrocyclization of a linear peptide and on-resin solid-phase macrocyclization with an acylsulfonamide safety-catch linker. The solution-phase route produced a mixture of proline rotamers, and the main component was assigned as the trans, cis rotamer, identical to the natural product. The on-resin cyclization was less successful, producing mainly a linear peptide, and minor cyclic products as rotameric mixtures. Although the natural product was reported to be significantly cytotoxic against Jurkat leukemia T cells, our synthetic peptides were inactive, suggesting the presence of other rotamers or impurities in the naturally isolated material. Additional analogues of zanriorb A1 were synthesized in which proline and glycine residues were replaced with alanine. While these analogues were not cytotoxic, several of them inhibited the production of nitric oxide in lipopolysaccharide (LPS)-stimulated macrophages. The most active compound, cyclic[Ala5,6,8 ]-zanriorb A1 had an IC50 of 22 µM and was more potent compared with the standard NG-monomethyl-l-arginine acetate (L-NMMA) with an IC50 of 98 µM, indicating their strong anti-inflammatory potential.

Burden of Drug resistant Tuberculosis in newly diagnosed Tuberculosis patients of Khyber Pakhtunkhwa, Pakistan.

OBJECTIVE: To explore the burden of drug-resistant tuberculosis in Khyber Pakhtunkhwa, Pakistan. METHODS: The cross-sectional study was conducted from March 1, 2016, to February 28, 2017, at the Khyber Pakhtunkhwa Tuberculosis Reference Laboratory, Hayatabad Medical Complex, Peshawar, Pakistan, and comprised referred suspected tuberculosis patient samples. Drug Susceptibility testing on all Mycobacterium tuberculosis complex strains was performed and data was subjected to statistical analysis. RESULTS: Of the 8220 samples, 4230 (51.5%) were related to females and 3990 (48.5%) to males. Also, 1978 (24%) were related to patients aged 15-24 years. Of the total, 1351 (16.5%) samples were positive on culture. Drug susceptibility testing showed 525 (39%) samples to be resistant to at least one of the first- and second-line drugs. Among the culture-positive cases, 5 (0.4%) were extensively drug-resistant, 62 (4.6%) multi-drug resistant, 243 (18%) polyresistant, 215 (16%) monoresistant and 826 (61%) were pan-sensitive. CONCLUSIONS: Drug-resistant tuberculosis in newly-diagnosed tuberculosis patients was alarmingly high in Khyber Pakhtunkhwa region.

Bacterial Spectrum and Antimicrobial Profile of Pediatric Blood Stream Infection at a Tertiary Care Hospital in Pakistan.

Objectives Blood stream infections (BSIs) are the main cause of morbidity and mortality in children worldwide. The present study was carried out to determine the prevalence of BSI with a focus on the identification of the causative agent of BSI, and to further evaluate the antibiotic susceptibility profile of the causing bacterial pathogens.Methods A cross-section study was carried out at the tertiary care hospital in Peshawar, Pakistan from January to December, 2018. Blood samples were collected in BACTECTM bottles and standard microbiological protocols were applied for the isolation and identification of bacterial strains. The antibiotic susceptibility tests were performed using disc diffusion method as per the 2014 guideline of Clinical Laboratory Standard Institute (CLSI).Results Of 567 blood cultures in total, 111(19.6%) were positive for BSI. Male children were 64 % (71/111) and female children were 36% (40/111). For the causative predominant group of microorganisms, Gram-negative bacteria were identified in 79 (71.1%) isolates, and Gram-positive bacteria in 32 (28.9%) isolates. The common bacteria of isolates were S. typhi (n=35, 31.5%), E. coli (n=19, 17.1%), S. aureus (n=18, 16.2%), K. pneumonia (n=12, 10.8%), and Enterococcus species (n=7, 6.3%). The 36.7% (29/79) isolates of Gram-negative bacteria were ESBL producers, and 61.1% (11/18) of S. aureus isolates were methicillin resistant. Overall, 72.9% isolates were multidrug resistant.Conclusions Gram-negative bacteria were the main cause of pediatric BSIs, where the predominant microorganism was S. typhi. Remarkably, majority of the S. typhi isolates were resistant to ciprofloxacin.

Determination of macro, micro, trace essential, and toxic elements in Garcinia cambogia fruit and its anti-obesity commercial products.

BACKGROUND: Garcinia (Clusiaceae) species are traditionally used as flavoring agents in curries and to cure several human health complications. This study investigated 31 macro, micro, and trace elements in microwave-assisted digested samples of Garcinia cambogia fruit and its anti-obesity commercial products by inductively coupled plasma-optical emission spectroscopy (ICP-OES) and inductively coupled plasma-mass spectrometric (ICP-MS) techniques. The methods were also validated using the coefficient of determination (R2 ), limits of detection and quantification (LOD, LOQ), precision (CV%), analysis of certified reference materials, spiking recovery experiments, and participation in an accredited laboratory proficiency test organized by Food Analysis Performance Assessment Scheme (FAPAS). RESULTS: Quality assurance confirmed that the methods were efficient and in accordance with criteria set by the Association of Official Analytical Chemists (AOAC). In the elemental analysis, the analyzed macro, micro, and trace essential elements were present in appreciable concentrations, which could meet the human nutritional requirements. Traces of toxic elements were within safe limits. CONCLUSION: From the results of the current study, the fruit and its commercial products could be considered potential sources of mineral elements without posing any threats to consumers. © 2018 Society of Chemical Industry.

Characterisation of breeding sites of anopheline mosquitoes in District Bannu, KPK, Pakistan.

OBJECTIVE: To highlight the role of habitat evaluation in reducing the potential transmission risk of malaria. METHODS: This study was conducted from January to June, 2015, in District Bannu in Khyber Pakhtunkhwa, Pakistan, where 64 larval habitats were characterised in 10 villages of the district. The larvae habitat features, like its permanent or temporary nature, artificial or natural, basic type, substrate type and vegetation, anopheline and culicine larval presence and density, were noted. ArcGIS 9.2 was used to map the mosquitoe breeding sites. Data was analysed related to the effect of temperature, rainfall and relative humidity on larval occurrence and density.. RESULTS: Of the 64 breeding habitats characterised, 26(40.6%) were temporary, while the remaining 38(59.4%) were permanent. Anopheline larvae were found in different types of habitats and occurred in man-made and temporary habitats with high population density. The marshlands (rice fields, sugarcane and open drains) were positive for anopheline larvae. The climatic factors like rain and humidity positively affected the larval density. The larval density was high in March and April at temperatures ranging from 16.1Co-23.45oC. CONCLUSIONS: Targeting the man-made and temporary larval habitats could results in the effective anopheline mosquitoes larvae control.

Investigation of potential sea level rise impact on the Nile Delta, Egypt using digital elevation models.

In this study, the future impact of Sea Level Rise (SLR) on the Nile Delta region in Egypt is assessed by evaluating the elevations of two freely available Digital Elevation Models (DEMs): the SRTM and the ASTER-GDEM-V2. The SLR is a significant worldwide dilemma that has been triggered by recent climatic changes. In Egypt, the Nile Delta is projected to face SLR of 1 m by the end of the 21th century. In order to provide a more accurate assessment of the future SLR impact on Nile Delta's land and population, this study corrected the DEM's elevations by using linear regression model with ground elevations from GPS survey. The information for the land cover types and future population numbers were derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) land cover and the Gridded Population of the Worlds (GPWv3) datasets respectively. The DEM's vertical accuracies were assessed using GPS measurements and the uncertainty analysis revealed that the SRTM-DEM has positive bias of 2.5 m, while the ASTER-GDEM-V2 showed a positive bias of 0.8 m. The future inundated land cover areas and the affected population were illustrated based on two SLR scenarios of 0.5 m and 1 m. The SRTM DEM data indicated that 1 m SLR will affect about 3900 km(2) of cropland, 1280 km(2) of vegetation, 205 km(2) of wetland, 146 km(2) of urban areas and cause more than 6 million people to lose their houses. The overall vulnerability assessment using ASTER-GDEM-V2 indicated that the influence of SLR will be intense and confined along the coastal areas. For instance, the data indicated that 1 m SLR will inundate about 580 Km(2) (6%) of the total land cover areas and approximately 887 thousand people will be relocated. Accordingly, the uncertainty analysis of the DEM's elevations revealed that the ASTER-GDEM-V2 dataset product was considered the best to determine the future impact of SLR on the Nile Delta region.

Cytotoxic benzophenone and triterpene from Garcinia hombroniana.

Garcinia hombroniana (seashore mangosteen) in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to investigate the bioactive chemical constituents of the bark of G. hombroniana. Ethyl acetate and dichloromethane extracts of G. hombroniana yielded two new (1, 9) and thirteen known compounds which were characterized by the spectral techniques of NMR, UV, IR and EI/ESI-MS, and identified as; 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone(1), 2,3',4,4'-tetrahydroxy-6-methoxybenzophenone (2), 2,3',4,6-tetrahydroxybenzophenone (3), 1,3,6,7-tetrahydroxyxanthone (4), 3,3',4',5,7-pentahydroxyflavone (5),3,3',5,5',7-pentahydroxyflavanone (6), 3,3',4',5,5',7-hexahydroxyflavone (7), 4',5,7-trihydroxyflavanone-7-rutinoside (8), 18(13→17)-abeo-3ß-acetoxy-9α,13ß-lanost-24E-en-26-oic acid (9), garcihombronane B (10), garcihombronane D (11), friedelan-3-one (12), lupeol (13), stigmasterol (14) and stigmasterol glucoside (15). In the in vitro cytotoxicity against MCF-7, DBTRG, U2OS and PC-3 cell lines, compounds 1 and 9 displayed good cytotoxic effects against DBTRG cancer cell lines. Compounds 1-8 were also found to possess significant antioxidant activities. Owing to these properties, this study can be further extended to explore more significant bioactive components of this plant.

Complete NMR assignments of bioactive rotameric (3 → 8) biflavonoids from the bark of Garcinia hombroniana.

The genus Garcinia is reported to possess antimicrobial, anti-inflammatory, anticancer, hepatoprotective and anti-HIV activities. Garcinia hombroniana in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to isolate the chemical constituents from the bark of G. hombroniana and explore their possible pharmacological potential. Ethyl acetate extract afforded one new (1) and six (2-7) known 3 → 8 rotameric biflavonoids. Their structures were elucidated by UV, IR and NMR (1D and 2D) spectroscopy together with electron ionization/ESI mass spectrometric techniques and were identified as (2R, 3S) volkensiflavone-7-O-rhamnopyranoside (1), volkensiflavone (2), 4″-O-methyl-volkensiflavone (3), volkensiflavone-7-O-glucopyranoside (4), morelloflavone (5), 3″-O-methyl-morelloflavone (6) and morelloflavone-7-O-glucopyranoside (7). The absolute configuration of compound 1 was assigned by circular dichroism spectroscopy as 2R, 3S. The coexistence of conformers of isolated biflavonoids in solution at 25 °C in different solvents was confirmed by variable temperature NMR studies. At room temperature (25 °C), compounds 1-7 exhibited duplicate NMR signals, while at elevated temperature (90 °C), a single set of signals was obtained. Compound 5 showed significant in vitro antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis-3-ethyl benzthiazoline-6-sulfonic acid radicals. The antibacterial studies showed that compounds 5 and 6 are the most active against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Compounds 3 and 6 also showed moderate antituberculosis activity against H38 Rv. Based on the research findings, G. hombroniana could be concluded as a rich source of flavanone-flavone (3 → 8) biflavonoids that exhibit rotameric behaviour at room temperature and display significant antioxidant and antibacterial activities.

Evaluation of diagnostic potential of Rv3803c and Rv2626c recombinant antigens in TB endemic country Pakistan.

To overcome and eliminate tuberculosis (TB), definitive, reliable, and rapid diagnosis is mandatory. Presently, the diagnostic potential of acute and latent stage TB specific antigens i.e., Rv3803c and Rv2626c was determined. Immunogenic recombinant genes of Rv3803c and Rv2626c antigens were cloned in bacterial expression vector pET23b and expressed product was purified. The homogeneity and structural integrity was confirmed by Western blot analysis. Diagnostic potential of Rv3803c and Rv2626c antigens was analyzed using the sera of 140 active TB patients (AFB smear positive) by indirect ELISA. Ten patients of leprosy and 94 healthy individuals were taken as disease and normal control respectively. The data was analyzed using R statistical package. The sensitivity and specificity of Rv3803c in active TB patients was of 69.3% and 76.4% respectively with an area under ROC curve of 0.77, whereas sensitivity and specificity of Rv2626c 77.1% and 85.1%, respectively. The area under ROC curve of Rv2626c was 0.89 which was significantly higher than Rv3803c (p < 0.0001). Recombinant antigens Rv3803c and Rv2626c have potential to be used as diagnostic markers for TB and need to evaluate with other antigens for differential diagnosis of TB.

Unraveling Impact of Hemoglobin F and A2 Levels: Correlation With Disease Severity and Treatment Response in Transfusion-Dependent Beta-Thalassemia.

BACKGROUND: Fetal hemoglobin (HbF) has been reported to be associated with disease severity and treatment response to HbF-inducing therapies like Hydroxyurea and thalidomide in patients suffering from transfusion-dependent beta-thalassemia (TDT). However, the role of hemoglobin A2 (HbA2) remains less clear in TDT, therefore this study aims to determine the impact of both HbF and HbA2 levels on disease severity and treatment response. METHODOLOGY: A prospective observational study was conducted at the Peshawar Institute of Medical Sciences and Fatimid Foundation Peshawar from May 2023 to October 2023. A total of 232 TDT-diagnosed patients were enrolled using a convenient sampling technique, whereas coinheritance of beta-thalassemia with other hemoglobinopathies was excluded. RESULT: This study reveals a significant impact of HbF on disease severity (p<0.05) but finds no substantial correlation (p>0.05) between HbA2 levels and disease severity. Additionally, HbF and HbA2 levels exhibit no association with treatment response categories in patients receiving HbF induction therapy, and various mutations do not significantly alter HbF and HbA2 levels or disease severity parameters in TDT patients. CONCLUSION: The study established a significant association between HbF and disease severity. However, regarding treatment response, neither HbF nor HbA2 levels impact response categories. Combinatorial treatment with hydroxyurea and thalidomide showed superior efficacy compared to monotherapy. A larger sample size and extended follow-up are recommended to further explore the impact of HbF, HbA2, and various mutations on disease severity and treatment response.

Exploring optimal drug targets through subtractive proteomics analysis and pangenomic insights for tailored drug design in tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, ranks among the top causes of global human mortality, as reported by the World Health Organization's 2022 TB report. The prevalence of M. tuberculosis strains that are multiple and extensive-drug resistant represents a significant barrier to TB eradication. Fortunately, having many completely sequenced M. tuberculosis genomes available has made it possible to investigate the species pangenome, conduct a pan-phylogenetic investigation, and find potential new drug targets. The 442 complete genome dataset was used to estimate the pangenome of M. tuberculosis. This study involved phylogenomic classification and in-depth analyses. Sequential filters were applied to the conserved core genome containing 2754 proteins. These filters assessed non-human homology, virulence, essentiality, physiochemical properties, and pathway analysis. Through these intensive filtering approaches, promising broad-spectrum therapeutic targets were identified. These targets were docked with FDA-approved compounds readily available on the ZINC database. Selected highly ranked ligands with inhibitory potential include dihydroergotamine and abiraterone acetate. The effectiveness of the ligands has been supported by molecular dynamics simulation of the ligand-protein complexes, instilling optimism that the identified lead compounds may serve as a robust basis for the development of safe and efficient drugs for TB treatment, subject to further lead optimization and subsequent experimental validation.

Whole-Exome sequencing identifies GYS2 biallelic variants in individuals with suspected epilepsy.

BACKGROUND: Adequate glucose supply is essential for brain function, therefore hypoglycemic states may lead to seizures. Since blood glucose supply for brain is buffered by liver glycogen, an impairment of liver glycogen synthesis by mutations in the liver glycogen synthase gene (GYS2) might result in a substantial neurological involvement. Here, we describe the phenotypes of affected siblings of two families harboring biallelic mutations in GYS2. METHODS: Two suspected families - a multiplex Pakistani family (family A) with three affected siblings and a family of Moroccan origin (family B) with a single affected child who presented with seizures and reduced fasting blood glucose levels were genetically characterized. Whole exome sequencing (WES) was performed on the index patients, followed by Sanger sequencing-based segregation analyses on all available members of both families. RESULTS: The variant prioritization of WES and later Sanger sequencing confirmed three mutations in the GYS2 gene (12p12.1) consistent with an autosomal recessive pattern of inheritance. A homozygous splice acceptor site variant (NM_021957.3, c. 1646 -2A>G) segregated in family A. Two novel compound heterozygous variants (NM_021957.3: c.343G>A; p.Val115Met and NM_021957.3: c.875A>T; p.Glu292Val) were detected in family B, suggesting glycogen storage disorder. A special diet designed to avoid hypoglycemia, in addition to change of the anti-seizure medication led to reduction in seizure frequency. CONCLUSIONS: This study suggests that the seizures in patients initially diagnosed with epilepsy might be directly caused, or influenced by hypoglycemia due to pathogenic variants in the GYS2 gene.

Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families.

Progressive myoclonic epilepsies (PMEs) are a group of neurodegenerative disorders, predominantly affecting adolescents and, characterized by generalized worsening myoclonus epilepsies, ataxia, cognitive deficits, and dementia. To date, several genes, having implications in diverse phenotypic expressions associated with PMEs, have been identified. Genetic diagnosis is available for most of the adolescence-onset myoclonic epilepsies. This study aimed to elucidate the genetic basis of PMEs in three multiplex Pakistani families exhibiting clinically variable phenotypes. Causative variant(s) in the studied families, and mode of segregation were identified by Whole Exome Sequencing (WES) of the probands, followed by bi-directional Sanger sequencing for final validation. We identified homozygous recessive CLN6 missense variant c.768 C>G (p.Asp256Glu) in Family 1, and c.889 C>A (p.Pro297Thr) variant in Family 2. While in Family 3, we found a homozygous variant (c.316dup) that caused a frameshift mutation, leading to a premature stop codon in the CLN6 protein, resulting in a truncated protein (p.Arg106ProfsTer26). Though CLN6 is previously identified to underlie late infantile and adolescent onset neuronal ceroid lipofuscinosis, this study supports and expands the phenotypic spectrum of CLN6 mutations and signifies diagnositc potential CLN6 variants for PMEs. Diverse pathological effects of variant c .768 C>G were observed in Family 1, with same genotypes, suggesting clinical heterogeneity and/or variable expressivity that might be the implication of pleiotropic effects of the gene in these cases.

Past and present of diagnosis of echinococcosis: A review (1999-2021).

The larval forms of taeniid cestodes belonging to the genus Echinococcus are the source of the zoonotic infection known as echinococcosis. Alveolar and cystic echinococcosis are caused by Echinococcus multilocularis and Echinococcus granulosus (s. s), respectively. It is endemic in several regions of the world. In this systematic review, we describe diagnosis, and the species (human, canids, livestock, and small rodents) affected by cystic (CE) and alveolar echinococcosis (AE). From 1999 to 2021, we searched the online directory through PubMed, SCOPUS, Web of Science, and google scholar. Among the 37,700 records found in the online databases, 187 publications met our eligibility requirements. The majority of investigations employed a range of diagnostic methods, such as ELISA, imaging, copro-PCR, necropsy or arecoline hydrobromide purgation, morphological cestode confirmation, and fecal sieving/flotation to detect and confirm Echinococcus infection. ELISA was the most commonly used method followed by PCR, and imaging. The research team retrieved data describing the incidence or assessment of the diagnostic test for E. multilocularis in humans (N = 99), canids (N = 63), small ruminants (N = 13), large ruminants (N = 3), camel (N = 2), pigs (N = 2) and small mammals (N = 5). This study was conducted to explore the diagnostic tools applied to detect echinococcosis in humans as well as animals in prevalent countries, and to report the characteristic of new diagnostic tests for disease surveillance. This systematic review revealed that ELISA (alone or in combination) was the most common method used for disease diagnosis and diagnostic efficacy and prevalence rate increased when recombinant antigens were used. It is highly recommended to use combination protcols such as serological with molecular and imaging technique to diagnose disease. Our study identified scarcity of data of reporting echinococcosis in humans/ animals in low-income or developing countries particularly central Asian countries. Study reports in small rodents indicate their role in disease dissemination but real situation in these host is not reflected due to limited number of studies. Even though echinococcosis affects both public health and the domestic animal sector, therefore, it is important to devise new and strengthen implementation of the existing monitoring, judging, and control measures in this estimate.

Mapping CircRNA-miRNA-mRNA regulatory axis identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection.

Non-coding RNAs (ncRNAs) can control the flux of genetic information; affect RNA stability and play crucial roles in mediating epigenetic modifications. A number of studies have highlighted the potential roles of both virus-encoded and host-encoded ncRNAs in viral infections, transmission and therapeutics. However, the role of an emerging type of non-coding transcript, circular RNA (circRNA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been fully elucidated so far. Moreover, the potential pathogenic role of circRNA-miRNA-mRNA regulatory axis has not been fully explored as yet. The current study aimed to holistically map the regulatory networks driven by SARS-CoV-2 related circRNAs, miRNAs and mRNAs to uncover plausible interactions and interplay amongst them in order to explore possible therapeutic options in SARS-CoV-2 infection. Patient datasets were analyzed systematically in a unified approach to explore circRNA, miRNA, and mRNA expression profiles. CircRNA-miRNA-mRNA network was constructed based on cytokine storm related circRNAs forming a total of 165 circRNA-miRNA-mRNA pairs. This study implies the potential regulatory role of the obtained circRNA-miRNA-mRNA network and proposes that two differentially expressed circRNAs hsa_circ_0080942 and hsa_circ_0080135 might serve as a potential theranostic agents for SARS-CoV-2 infection. Collectively, the results shed light on the functional role of circRNAs as ceRNAs to sponge miRNA and regulate mRNA expression during SARS-CoV-2 infection.

Applications of Metformin in Dentistry-A review.

Metformin is a versatile drug with numerous medical uses. It is known primarily as an anti-hyperglycemic drug that has become the main oral blood-glucose-lowering medication for managing type 2 diabetes mellitus globally. Its use has been reported in a variety of oral conditions and dentistry in general. Recent clinical trials have indicated the effectiveness of adjunct topical application of metformin in improving the periodontal parameters of patients with diabetes and periodontitis. Additionally, studies have suggested that metformin stimulates odontogenic differentiation and mineral synthesis of stem cells in the tooth pulp. Metformin also stimulates osteoblast proliferation, decreases osteoclast activity and exerts regenerative effects on periodontal bone, thus making it a viable candidate for periodontal regeneration. Metformin monotherapy significantly enhances osseointegration of endosseous implants and has been reported to have anti-cancer effects on oral squamous cell carcinoma by impeding tumor progression. Animal studies have indicated that metformin improves orthodontic tooth movement and resists orthodontic appliance corrosion. This narrative review aims to provide a current summary of research highlighting the prospective uses of metformin in dentistry.

Development of a Real-Time qPCR Assay for Detection of Common MPL Mutations in Myeloproliferative Neoplasms (MPNS).

Myeloproliferative neoplasms (MPNs) are blood cell disorders, characterized by overproduction of abnormal cells in bone marrow due to stem cell mutation. The proliferations of blood cell are controlled by many genes particularly MPL gene which encodes thrombopoietin receptor, a hematopoietic growth factor involved in the production and regulation of the platelets and multipotent hematopoietic progenitor cells. Acquired mutations including (W515L and W515K) in this gene have been observed in patients with primary myelofibrosis or essential thrombocythemia lacking JAK2 (V617F) mutations. MPL mutation detection is important for MPNs diagnosis, but due to low frequency of mutant allele burden (< 15%) may be missed by already available common assays such as Sanger sequencing. Furthermore, these techniques are costly, time-consuming, and less sensitive. In present study, we aimed to develop sensitive, less time-consuming, and cost-effective real-time PCR assay for the detection of MPL mutations that is based on TaqMan fluorescent probes. DNA was extracted from blood sample of 128 MPNs patients collected and further analysis was performed on TaqMan RT-PCR. Reference curve was obtained for amplified product of MPL gene containing mutated sequence. The predicted sensitivity level was at least 5% mutant allele burden by our developed assay that is much higher than sequencing output. Out of 128, 2 (1.56%) patients harbored W515L mutation and 1 (0.78%) harbored W515K mutation. It was concluded that TaqMan qRT-PCR assay is an efficient, sensitive, cost-effective, and less time-consuming method capable of detecting MPL mutation in MPNs patients. We suggested that this assay might be helpful in investigating mutant allele load in MPNs patients.

Fibroblast growth factor 2 is a druggable target against glioblastoma: A computational investigation.

Fibroblast growth factor 2 (FGF2) is a key player in cancer and tissue homeostasis and regulates renewal of several stem cell types. The FGF2 role in malignant glioma is proven and tagged FGF2, a novel druggable target, is used for developing potent drugs against glioblastoma. In this study, Asinex 51412372, Asinex 51217461, and Asinex 51216586 were filtered to show the best binding affinity for FGF2 with binding energy scores of -8.3 kcal/mol, -8.2 kcal/mol, and -7.8 kcal/mol, respectively. The compounds showed chemical interactions with several vital residues of FGF2 along the compound length. The noticeable residues that interacted with the compounds were Arg15, Asp23, Arg63, and Gln105. In dynamic investigation in solution, the FGF2 reported unstable dynamics in the first 100 ns and gained structural equilibrium in the second phase of 100 ns. The maximum root mean square deviation (RMSD) value touched by the systems is 3 Å. Similarly, the residue flexibility of FGF2 in the presence of compounds was within a stable range and is compact along the simulation time length. The compounds showed robust atomic-level stable energies with FGF2, which are dominated by both van der Waals and electrostatic interactions. The net binding energy of systems varies between -40 kcal/mol and -86 kcal/mol, suggesting the formation of strong intermolecular docked complexes. The drug-likeness and pharmacokinetic properties also pointed toward good structures that are not toxic, have high gastric absorption, showed good distribution, and readily excreted from the body. In summary, the predicted compounds in this study might be ideal hits that might be further optimized for structure and activity during experimental studies.

Herbal Medicines against Hydatid Disease: A Systematic Review (2000-2021).

Echinococcosis is a serious public health issue that affects people and livestock all over the world. Many synthetic and natural products have been examined in vitro and in vivo on Echinococcus species but only a few are used clinically, however, they may cause some complications and side effects. To overcome these limitations, new horizons of herbal drugs to cure echinococcosis are opening with every passing day. To summarize the developments during the last 21 years, we conducted this review of the literature to identify medicinal herbs utilized throughout the world that have anti-Echinococcus activity. From 2000 to 2021, data were carefully obtained from four English databases: Science Direct, PubMed, Scopus, and OpenGrey. Botanical name, extraction technique, extract quantities, efficacy, duration of treatment, year of publication, and half-maximal inhibitory concentration (IC50) values were all well noted. Ninety-one published papers, with 78 in vitro and 15 in vivo, fulfilled our selection criteria. Fifty-eight different plant species were thoroughly tested against Echinococcus granulosus. Zataria multiflora, Nigella sativa, Berberis vulgaris, Zingiber officinale (ginger), and Allium sativum were the most often utilized anti-Echinococcus herbs and the leaves of the herbs were extensively used. The pooled value of IC50 was 61 (95% CI 60−61.9) according to the random effect model and a large degree of diversity among studies was observed. The current systematic study described the medicinal plants with anti-Echinococcus activity, which could be investigated in future experimental and clinical studies to identify their in vivo efficacy, lethal effects, and mechanisms of action.