Linalool-zinc oxide nanocomposite controls Toxoplasma gondii infection through inhibiting inflammation, oxidative stress, and pathogenicity.

The present in vitro and in vivo study aimed to fabricate and characterize linalool-zinc oxide nanoparticles (Lin-ZNP) and evaluate their effectiveness against Toxoplasma gondii infection in terms of inflammation, oxidative stress, and pathogenicity. Lin-ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The anti-Toxoplasma and cytotoxicity activities of Lin-ZNP were investigated, along with its effects on nitric oxide (NO) production, caspase-3 activity, and pro-inflammatory genes. After treating T. gondii-infected mice with Lin-ZNP for 14 days, the number and size of tissue cysts, antioxidant potential, pro-inflammatory cytokines, and T. gondii pathogenicity-related genes were evaluated by real-time polymerase chain reaction and Western blot analysis. The Lin-ZNP composite showed a reduced tendency with an average size of 105 nm. Lin-ZNP significantly reduced the viability of tachyzoites. The obtained selectivity index higher than 10, indicating high specificity for parasites with low cytotoxicity to normal cells. The Lin-ZNP significantly (p < 0.05) increased the production of NO, caspase-3 activity, and the expression levels of pro-inflammatory genes. Lin-ZNP significantly (p < 0.001) decreased the size and number of tissue cysts and caused a significant reduction in the level of malondialdehyde and a considerable increase (p < 0.001) in antioxidant enzymes and their expression genes. Lin-ZNP significantly downregulated both mRNA and protein expression of the inflammation-related markers associated with the TLRs/NF-κB pathway. The expression levels of the T. gondii pathogenicity-related genes were significantly downregulated (p < 0.05). The recent survey indicated that Lin-ZNP manages T. gondii infection by its antioxidant activity and inhibiting the TLRs/NF-κB pathway without toxicity in mice.

High potency of linalool-zinc oxide nanocomposite as a new agent for cystic echinococcosis treatment.

This current in vitro, ex vivo, and in vivo research aims to evaluate and analyze the linalool-zinc oxide nanocomposite (Lin-ZNP) for treating cystic echinococcosis. Lin-ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The protoscolicidal effects of Lin-ZNP were tested on hydatid cyst protoscoleces (PTS) in both in vitro and ex vivo by eosin exclusion test. The study also examined the impact on caspase-3 gene expression and the external structure of PTS. The in vivo effect was measured by examining hydatid cysts' quantity, dimensions, and weight in mice intraperitoneally infected with 0.5 mL of PTS solution containing 1,000 PTS. The antioxidant and inflammatory cytokine gene expression levels were examined using real-time PCR. Lin-ZNP significantly (P < 0.001) killed the PTS in both in vitro and ex vivo in a dose- and time-dependent manner. The treated PTS exhibited creases and protrusions as a result of bleb formation and upregulation in the gene expression of caspase-3. Upon treatment with Lin-ZNP, there was a significant (P < 0.001) reduction in the number, diameter, and weight of the hydatid cysts. Treatment with Lin-ZNP nanocomposite led to a significant increase in the expression of antioxidant genes and a notable decrease in oxidative stress markers, and the expression levels of IL-4 and IL-10. Lin-ZNP has the potential to act as a scolicidal agent and demonstrates promise in controlling hydatid cysts in a mouse model, attributed to its antioxidant and anti-inflammatory properties. However, additional studies in clinical trials are needed to confirm the use of Lin-ZNP for treating hydatidosis.

High Efficacy of Green Synthesized Silver Nanoparticles for Treatment of Toxoplasma Gondii Infection Through Their Immunomodulatory, Anti-Inflammatory, and Antioxidant Potency.

The present experimental survey designed to green synthesis, characterization, as well as in vitro and in vivo anti-Toxplasma gondii activity of silver nanoparticles (SLN) green synthesized by Lupinus arcticus extract. SLN were green synthesized based on the reducing by L. arcticus extract through the precipitation technique. In vitro lethal effects of SLN on T. gondii tachyzoites, infectivity rate, parasites inside of the human macrophage cells (THP-1 cells), nitric oxide (NO) triggering, and iNOS and interferon gamma (IFN-γ) expression genes were evaluated. In vivo, after establishment of toxoplasmosis in BALB/c mice via T. gondii ME49 strain, mice received SLN at 10 and 20 mg/kg/day alone and combined to pyrimethamine at 5 mg/kg for 14 days. SLN exhibited a spherical form with a size ranging from 25 to 90 nm. The 50% inhibitory concentration (IC50) value of SLN and pyrimethamine against tachyzoites was 29.1 and 25.7 µg/mL, respectively. While, the 50% cytotoxic concentration (CC50) value of SLN and pyrimethamine against THP-1 cells was 412.3 µg/mL and 269.5 µg/mL, respectively. SLN in combined with pyrimethamine obviously (p < 0.05) decreased the number and size of the T. gondii cysts in the infected mice. The level of NO, iNOS and IFN-γ genes was obviously (p < 0.001) upregulated. SLN obviously (p < 0.05) decreased the liver level of oxidative stress and increased the level of antioxidant factors. The findings displayed the promising beneficial effects of SLN mainly in combination with current synthetic drugs against latent T. gondii infection in mice. But we need more experiments to approve these findings, clarifying all possible mechanisms, and its efficiency in clinical phases.

Unveiling of the antileishmanial activities of Linalool loaded zinc oxide nanocomposite through its potent antioxidant and immunomodulatory effects.

This study aimed to produce linalool loaded zinc oxide nanocomposite (LZNPs) and assess its in vitro and in vivo antileishmanial effects against Leishmania major. LZNPs was produced through the synthesis of an ethanolic solution containing polyvinyl alcohol. The average size of LZNPs was determined to be 105 nm. The findings indicated that LZNPs displayed significant (p < 0.01) antileishmanial effects on promastigotes and amastigotes. Following exposure of promastigotes to LZNPs, there was a notable rise in the percentage of early and late apoptotic cells from 9.0 to 57.2 %. The gene expression levels of iNOS, IFN-γ, and TNF-α in macrophages were upregulated in a dose-dependent approach following exposure to LZNPs. LZNPs alone and in conjunction with glucantime (Glu) resulted in a reduction in the diameter and parasite load of CL lesions in infected mice. Treatment of the CL-infected mice with LZNPs at 25 and 50 mg/kg mainly in combination with Glu-reduced the tissue level of malondialdehyde (MDA), increased both gene and protein expression of the antioxidant enzymes as well as raised the expression level of IFN-γ and IL-12 cytokines, whereas caused a significant reduction in the expression level of IL-4. The present study shows that LZNPs has potent antileishmanial effects and controls CL in a mice model through its antioxidant and immunomodulatory properties. Further investigation, especially in clinical trials, could explore the potential use of this nanocomposite in managing and treating CL.

Structural Exploration of the PfBLM Helicase-ATP Binding Domain and Its Implications in the Quest for Antimalarial Therapies.

BACKGROUND OBJECTIVES: The battle against malaria has witnessed remarkable progress in recent years, characterized by increased funding, the development of life-saving tools, and a significant reduction in disease prevalence. Yet, the formidable challenge of drug resistance persists, threatening to undo these gains. METHODS: To tackle this issue, it is imperative to identify new effective drug candidates against the malaria parasite and exhibit minimal toxicity. This study focuses on discovering such candidates by targeting PfRecQ1, also known as PfBLM, a vital protein within the malaria parasite. PfRecQ1 plays a crucial role in the parasite's life cycle and DNA repair processes, making it an attractive drug development target. The research employs advanced computational techniques, including molecular modeling, structure-based virtual screening (SBVS), ADMET profiling, molecular docking, and dynamic simulations. RESULTS: The study sources ligand molecules from the extensive MCULE database and utilizes strict filters to ensure the compounds meet essential criteria. Through these techniques, the research identifies MCULE-3763806507-0-9 as a promising anti-malarial drug candidate, surpassing the binding affinity of potential antimalarial drugs. However, it is essential to underscore that the drug-like properties are primarily based on in silico experiments, and wet lab experiments are necessary to validate these candidates' therapeutic potential. INTERPRETATION CONCLUSION: This study represents a critical step in addressing the challenge of drug resistance in the fight against malaria.

Enumeration of olive derived lignan, pinoresinol for activity against recent Omicron variant spike protein for structure-based drug design, DFT, molecular dynamics simulations, and MMGBSA studies.

The coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, in December 2019. Because the virus spreads quickly, it quickly became a global worry. Coronaviridae is the family that contains both SARS-CoV-2 and the viruses that came before (i.e., MERS-CoV and SARS-CoV). Recent sources portray that the COVID-19 virus has affected 344,710,576 people worldwide and killed about 5,598,511 people in the last 2 years. The B.1.1.529 strain, later called "Omicron," was named a Variant of Concern on November 24, 2021. The SARS-CoV-2 virus has gone through a never-ending chain of changes that have never happened before. As a result, it has many different traits. Most of these changes have occurred in the spike protein, where antibodies bind. Because of these changes, the Omicron type is very contagious and easy to pass on. There have been a lot of studies done to try to figure out this new challenge in the COVID-19 strains race, but there is still a lot that needs to be explained. This study focuses on virtual screening, docking, and molecular dynamic analysis; we aimed to identify therapeutic candidates for the SARS-CoV-2 variant Omicron based on their ability to inhibit non-structural proteins. We investigate the prediction of the properties of a substantial database of drug molecules obtained from the OliveNet™ database. Compounds that did not exhibit adequate gastrointestinal absorption and failed the Lipinski test are not considered for further research. The filtered compounds were coupled with our primary target, SARS-CoV-2 Omicron spike protein. We focused on SARS-CoV-2 Omicron spike protein and filtering potent olive compounds. Pinoresinol, the most likely candidate, is bound best (- 8.5 kcal/mol). Pinoresinol's strong interaction with the active site made the complex's dynamic structure more resilient. MD simulations explain the protein-ligand complex's stability and function. Pinoresinol may be a promising SARS-CoV-2 Omicron spike protein receptor lead drug, and additional research may assist the scientific community.

Antimalarial drug discovery against malaria parasites through haplopine modification: An advanced computational approach.

The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by Plasmodium spp., which includes Apicoplast DNA polymerase and Plasmodium falciparum cysteine protease falcipain-2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti-malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand-protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross-correlation matrix showed positive outcomes for the protein-ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.

HARD TICKS (ACARI: IXODIDAE) INFESTING ARABIAN CAMELS (CAMELUS DROMEDARIUS) IN MEDINA AND QASSIM, SAUDI ARABIA.

Ixodid ticks are hematophagous obligatory ectoparasites that occur worldwide and transmit pathogens to humans and other vertebrates, causing economic livestock losses. The Arabian camel (Camelus dromedarius Linnaeus, 1758) is an important livestock animal in Saudi Arabia that is vulnerable to parasitism by ticks. The diversity and intensity of ticks on Arabian camels in certain localities in the Medina and Qassim regions of Saudi Arabia were determined. One hundred forty camels were examined for ticks, and 106 were infested (98 females, 8 males). A total of 452 ixodid ticks (267 males, 185 females) were collected from the infested Arabian camels. The tick infestation prevalence was 83.1% and 36.4% in female and male camels, respectively (female camels harbored significantly more ticks than did male camels). The recorded tick species were Hyalomma dromedarii Koch, 1844 (84.5%); Hyalomma truncatum Koch, 1844 (11.1%); Hyalomma impeltatum Schulze and Schlottke, 1929 (4.2%); and Hyalomma scupense Schulze, 1919 (0.22%). Hyalomma dromedarii was the predominant tick species in most regions, with a mean intensity of 2.15 ± 0.29 ticks/camel (2.5 ± 0.53 male ticks/camel, 1.8 ± 0.21 female ticks/camel). The proportion of male ticks was higher than that of female ticks (59.1 vs. 40.9%). To the best of our knowledge, this is the first survey of ixodid ticks on Arabian camels in Medina and Qassim, Saudi Arabia.

Mutations in FGFR1 were associated with growth traits in sheep (Ovis aries).

For its role in the mediation of myoblast proliferation, fibroblast growth factor receptor 1 (FGFR1) was considered a functional candidate gene for growth performance in Tibetan sheep. Via the polymerase chain reaction-restriction fragment length polymorphism (PCR-PFLP) approach, four single nucleotide polymorphisms (SNPs) including g.14752C > T (intron 1), g.45361A > G (intron 7), g.49400A > G (3'UTR region) and g.49587A > T (3'UTR region), were identified in 422 ewes. The association analysis demonstrated that individuals carrying the AA genotype of g.49400A > G had significantly greater withers height, length than those with GG genotype (p < 0.05). Individuals with genotype AA of g.49587A > T had significantly greater weight and chest circumference than those with genotype TT (p < 0.01). Additionally, the individuals with Hap1/1 diplotypes (CAAA-CAAA) were highly significantly associated with weight and chest circumference than Hap1/2 diplotypes (CAAA-CAAT) (p < 0.05). The quantitative real-time polymerase chain reaction (qPCR) analysis revealed that the FGFR1 was detectable expressed in muscle tissues within three different age stage. Remarkably higher mRNA expression was detected at fetal lamb stage as compared with adult ewes (p < 0.01). The outcome of this research confirmed that both g.49400A > G and g.49587A > T of FGFR1 were involved in growth-related traits, which may be considered to be genetic markers for improving the growth traits of Tibetan sheep.

Bioinformatics role of the WGCNA analysis and co-expression network identifies of prognostic marker in lung cancer.

Lung cancer is the most talked about cancer in the world. It is also one of the cancers that currently has a high mortality rate. The aim of our research is to find more effective therapeutic targets and prognostic markers for human lung cancer. First, we download gene expression data from the GEO database. We performed weighted co-expression network analysis on the selected genes, we then constructed scale-free networks and topological overlap matrices, and performed correlation modular analysis with the cancer group. We screened the 200 genes with the highest correlation in the cyan module for functional enrichment analysis and protein interaction network construction, found that most of them focused on cell division, tumor necrosis factor-mediated signaling pathways, cellular redox homeostasis, reactive oxygen species biosynthesis, and other processes, and were related to the cell cycle, apoptosis, HIF-1 signaling pathway, p53 signaling pathway, NF-κB signaling pathway, and several cancer disease pathways are involved. Finally, we used the GEPIA website data to perform survival analysis on some of the genes with GS > 0.6 in the cyan module. CBX3, AHCY, MRPL12, TPGB, TUBG1, KIF11, LRRC59, MRPL17, TMEM106B, ZWINT, TRIP13, and HMMR was identified as an important prognostic factor for lung cancer patients. In summary, we identified 12 mRNAs associated with lung cancer prognosis. Our study contributes to a deeper understanding of the molecular mechanisms of lung cancer and provides new insights into drug use and prognosis.

Potential Therapeutic Candidates against Chlamydia pneumonia Discovered and Developed In Silico Using Core Proteomics and Molecular Docking and Simulation-Based Approaches.

Chlamydia pneumonia, a species of the family Chlamydiacea, is a leading cause of pneumonia. Failure to eradicate C. pneumoniae can lead to chronic infection, which is why it is also considered responsible for chronic inflammatory disorders such as asthma, arthritis, etc. There is an urgent need to tackle the major concerns arising due to persistent infections caused by C. pneumoniae as no FDA-approved drug is available against this chronic infection. In the present study, an approach named subtractive proteomics was employed to the core proteomes of five strains of C. pneumonia using various bioinformatic tools, servers, and software. However, 958 non-redundant proteins were predicted from the 4754 core proteins of the core proteome. BLASTp was used to analyze the non-redundant genes against the proteome of humans, and the number of potential genes was reduced to 681. Furthermore, based on subcellular localization prediction, 313 proteins with cytoplasmic localization were selected for metabolic pathway analysis. Upon subsequent analysis, only three cytoplasmic proteins, namely 30S ribosomal protein S4, 4-hydroxybenzoate decarboxylase subunit C, and oligopeptide binding protein, were identified, which have the potential to be novel drug target candidates. The Swiss Model server was used to predict the target proteins' three-dimensional (3D) structure. The molecular docking technique was employed using MOE software for the virtual screening of a library of 15,000 phytochemicals against the interacting residues of the target proteins. Molecular docking experiments were also evaluated using molecular dynamics simulations and the widely used MM-GBSA and MM-PBSA binding free energy techniques. The findings revealed a promising candidate as a novel target against C. pneumonia infections.

Acaricidal, Larvacidal, and Repellent Activity of Elettaria cardamomum Essential Oil against Hyalomma anatolicum Ticks Infesting Saudi Arabian Cattle.

Background: In this experimental study, we aimed to assess the acaricidal effects of Elettaria cardamomum L. essential oil (ECEO) against Hyalomma anatolicum tick in cattle from Saudi Arabia. Methods: Gas chromatography-mass spectrometry (GC-MS) was performed to identify the chemical composition of ECEO. The acaricidal, larvicidal, and repellent activity of ECEO against H. anatolicum was studied through the adult immersion test (AIT), the larval packet test (LPT), the vertical movement behavior of tick's larvae technique, anti-acetylcholinesterase (AChE) activity, and oxidative enzyme activity. Results: By GC/MS, the most compounds were 1,8-cineole (34.3%), α-terpinyl acetate (23.3%), and α-pinene (17.7%), respectively. ECEO significantly (p < 0.001) increased the mortality rate as a dose-dependent response. After ECEO Treatment, number of eggs, egg weight, and hatchability significantly declined as a dose-dependent response. ECEO at concentrations of 5 µL/mL and above completely killed the larva. The LC50 and LC90 values for ECEO were 1.46 and 2.68 µL/mL, respectively. ECEO at concentrations of 10, 20, and 40 µL/mL showed 100% repellency activity up to 60, 120, and 360 min incubation, respectively. ECEO, especially at ½ LC50 and LC50, significantly inhibited GST and AChE activities of H. anatolicum larvae compared to the control group. Conclusions: We found promising adulticidal, larvicidal, and repellent effects of ECEO against H. anatolicum as a vector of theileriosis in Saudi Arabia. We also found that ECEO displayed these activities through inhibiting AChE and GST. Nevertheless, additional investigations are required to confirm the accurate mechanisms and the relevance of ECEO in practical application.

Predicting Intensive Care Unit Admission for COVID-19 Patients from Laboratory Results.

Trends in routine laboratory tests, such as high white blood cell and low platelet counts, correlate with COVID-19-related intensive care unit (ICU) admissions. Other related biomarkers include elevated troponin, alanine aminotransferase, and aspartate transaminase levels (liver function tests). To this end, the aim of this study was to investigate the effect of changes in laboratory test parameters on ward-based and ICU COVID-19 patients. A total of 280 COVID-19 patients were included in the study and were divided based on admission status into ICU (37) or ward (243) patients. ICU admission correlated significantly with higher levels of several tested parameters, including lactate dehydrogenase, creatinine, D-dimer, creatine kinase, white blood cell count, and neutrophil count. In conclusion, routine laboratory tests offer an indication of which COVID-19 patients are most likely to be admitted to the ICU. These associations can assist healthcare providers in addressing the needs of patients who are at risk of COVID-19 complications.

Anticancer, antioxidant, antiviral and antimicrobial activities of Kei Apple (Dovyalis caffra) fruit.

Secondary plant metabolites remain one of the key sources of therapeutic agents despite the development of new approaches for the discovery of medicinal drugs. In the current study, chemical analysis, and biological activities of Kei apple (Dovyalis caffra) methanolic extract were evaluated. Chemical analysis was performed using HPLC and GC-MS. Antiviral and anticancer effect were assessed using the crystal violet technique and activity against human liver cells (HepG2), respectively. Antibacterial activity was tested with the disc diffusion method. The obtained results showed that chlorogenic acid (2107.96 ± 0.07 µg/g), catechin (168 ± 0.58 µg/g), and gallic acid (15.66 ± 0.02 µg/g) were the main bioactive compounds identified by HPLC techniques. While, compounds containing furan moieties, as well as levoglucosenone, isochiapin B, dotriacontane, 7-nonynoic acid and tert-hexadecanethiol, with different biological activities were identified by GC-MS. Additionally, inhibition of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) scavenging was 79.25% at 2000 µg/mL, indicating its antioxidant activity with IC50 of 728.20 ± 1.04 µg/mL. The tested extract exhibited potential anticancer activity (58.90% toxicity) against HepG2 cells at 1000 µg/mL. Potential bacterial inhibition was observed mainly against Escherichia coli and Proteus vulgaris, followed by Staphylococcus aureus and Bacillus subtilis with a diameter of growth inhibition ranging from 13 to 24 mm. While weak activities were recorded for fungi Candida albicans (10 mm). The extract showed mild antiviral activity against human coronavirus 229E with a selective index (SI) of 10.4, but not against human H3N2 (SI of 0.67). The molecular docking study's energy ratings were in good promise with the experiment documents of antibacterial and antiviral activities. The findings suggest that D. caffra juice extract is a potential candidate for further experiments to assess its use as potential alternative therapeutic agent.

Immunomodulatory Efficacy-Mediated Anti-HCV and Anti-HBV Potential of Kefir Grains; Unveiling the In Vitro Antibacterial, Antifungal, and Wound Healing Activities.

The utilization of fermented foods with health-promoting properties is becoming more popular around the world. Consequently, kefir, a fermented milk beverage made from kefir grains, was shown in numerous studies to be a probiotic product providing significant health benefits. Herein, we assessed the antibacterial and antifungal potential of kefir against a variety of pathogenic bacteria and fungi. This study also showed the effectiveness of kefir in healing wounds in human gastric epithelial cells (GES-1) by (80.78%) compared with control (55.75%) within 48 h. The quantitative polymerase chain reaction (qPCR) results of kefir-treated HCV- or HBV- infected cells found that 200 µg/mL of kefir can eliminate 92.36% of HCV and 75.71% of HBV relative to the untreated infected cells, whereas 800 µg/mL (the highest concentration) completely eradicated HCV and HBV. Moreover, the estimated IC50 values of kefir, at which HCV and HBV were eradicated by 50%, were 63.84 ± 5.81 µg/mL and 224.02 ± 14.36 µg/mL, correspondingly. Kefir can significantly suppress the elevation of TNF-α and upregulate IL-10 and INF-γ in both treated HCV- and HBV-infected cells. High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analysis of kefir revealed the presence of numerous active metabolites which mainly contribute to the antimicrobial, antiviral, and immunomodulatory activities. This study demonstrated, for the first time, the anti-HBV efficacy of kefir while also illustrating the immunomodulatory impact in the treated HBV-infected cells. Accordingly, kefir represents a potent antiviral agent against both viral hepatitis C and B, as well as having antimicrobial and wound healing potential.

Laboratory Biomarkers Associated with Severity and Mortality of COVID-19.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) emerged late 2019 and has become a global pandemic. There is an urgent need for identification of biomarkers to predict severity of the disease for early treatment and to avoid mortality especially in high-risk population. Therefore, the aim of this study is to investigate laboratory results in COVID-19 patients in Saudi Arabia to identify potential biomarkers correlated with disease severity. METHODS: Clinical records of 200 patients diagnosed with COVID-19 from July to August 2020 at Jeddah East Hospital were retrospectively analyzed. Laboratory tests including coagulation parameters, D-dimer, kidney, cardiac, and liver enzymes were statistically investigated in patients admitted to wards and intensive care units (ICU). RESULTS: The majority of patients admitted to ward (156/200) were young (mean 47 years old) compared to those admitted to ICU (mean 60 years old), 14/44 passed away in the ICU. Magnesium was significantly (p < 0.05) elevated in the ICU group while blood urea nitrogen and creatinine level was significantly higher in deceased patients (p < 0.05). Lactate dehydrogenase results were high among all groups, compared to normal range, although its level significantly increased (p > 0.05) in ICU and death groups. CONCLUSIONS: Elevated lactate dehydrogenase, blood urea nitrogen and creatinine levels may increase the risk of ICU admission and death from COVID-19, which can be used as potential biomarkers for disease severity. Using these markers could help physicians choose the optimal therapeutical option and provide patients with better treatment.

Construction of Adipogenic ceRNA Network Based on lncRNA Expression Profile of Adipogenic Differentiation of Human MSC Cells.

The Long non-coding RNA (lncRNA) expression profile data of ten samples including human Mesenchymal Stem Cell (MSC) adipogenic differentiation 0, 3, and 6 days from the GEO database, and then perform gene ID conversion, BLAST comparison, and annotation marking. Finally, group A (treatment group on day 3 of differentiation and control group on day 0 of differentiation) obtained a total of 1180 mRNA and 185 lncRNA; group B (treatment group on day 6 of differentiation and control group on day 0 of differentiation). A total of 1376 mRNA and 206 lncRNA were obtained. Finally, we processed the differential lncRNAs and mRNAs obtained in the two groups, and obtained 113 shared differential lncRNAs to further predict the targeted miRNA, a total of 815 lncRNA-miRNA pairs. The targeted mRNA was further predicted, and the grouped differential mRNAs were combined to obtain 64 differential mRNAs. In the end, we obtained 216 ceRNAs containing 26 lncRNAs, 27 miRNAs and 64 mRNAs. We found that the mRNAs in the ceRNA network were mainly enriched with 45 Gene Ontology (GO) terms, mainly including glucose homeostasis mechanism and insulin stimulation response. 69 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were mainly enriched. It mainly includes many pathways related to lipid metabolism such as Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), Rap1, cAMP, mitogen-activated protein kinase (MAPK), Ras, hypoxia inducible factor-1 (HIF-1), PI3K-Akt, insulin signaling and so on. In the end, we identified 216 ceRNA regulatory relationships related to obesity research. Our research provides a clearer direction for understanding the molecular mechanism of obesity, the screening and determination of drug targets biomarkers in the future.

Screening and Identification of Muscle-Specific Candidate Genes via Mouse Microarray Data Analysis.

Muscle tissue is involved with every stage of life activities and has roles in biological processes. For example, the blood circulation system needs the heart muscle to transport blood to all parts, and the movement cannot be separated from the participation of skeletal muscle. However, the process of muscle development and the regulatory mechanisms of muscle development are not clear at present. In this study, we used bioinformatics techniques to identify differentially expressed genes specifically expressed in multiple muscle tissues of mice as potential candidate genes for studying the regulatory mechanisms of muscle development. Mouse tissue microarray data from 18 tissue samples was selected from the GEO database for analysis. Muscle tissue as the treatment group, and the other 17 tissues as the control group. Genes expressed in the muscle tissue were different to those in the other 17 tissues and identified 272 differential genes with highly specific expression in muscle tissue, including 260 up-regulated genes and 12 down regulated genes. is the genes were associated with the myofibril, contractile fibers, and sarcomere, cytoskeletal protein binding, and actin binding. KEGG pathway analysis showed that the differentially expressed genes in muscle tissue were mainly concentrated in pathways for AMPK signaling, cGMP PKG signaling calcium signaling, glycolysis, and, arginine and proline metabolism. A PPI protein interaction network was constructed for the selected differential genes, and the MCODE module used for modular analysis. Five modules with Score > 3.0 are selected. Then the Cytoscape software was used to analyze the tissue specificity of differential genes, and the genes with high degree scores collected, and some common genes selected for quantitative PCR verification. The conclusion is that we have screened the differentially expressed gene set specific to mouse muscle to provide potential candidate genes for the study of the important mechanisms of muscle development.

Risk factor analysis for the prevalence of gastrointestinal parasites found in large ruminants in Lower Dir Khyber Pakhtunkhwa Pakistan.

The present study was designed to investigate the prevalence of gastrointestinal (GI) parasites in cattle and buffaloes of Lower Dir Khyber Pakhtunkhwa, Pakistan. The presence of the eggs, cysts, and oocysts of GI parasites in fecal samples were detected using direct smear methods and concentration techniques including floatation, centrifugation, and sedimentation. Identification of recovered fecal stages were determined by morphology using size and appearance of the recovered eggs, cysts, and oocysts. A total of 314 fecal samples were collected from the different Tehsils (Administrative Districts) and analyzed through microscopy. A higher prevalence was observed in the buffalo than the cow population. A total of 184 samples were positive for GI parasites of which 109/196 (55.61%) were from cattle, whereas 75/118 (63.55%) were from buffaloes. The minimum number of strongyle eggs detected in all the samples were 136.39 eggs/g (EPG). The mean EPG in cattle was 143.30 and 122.56 in buffaloes. The open-source water prevalence of GI parasites was higher than the other sources in cattle and the second highest after tap water in buffaloes. The seasonal prevalence of GI parasites ranged from 32.39% (23/71), in spring to 68.8% (86/125) in summer in cattle. In was For buffaloes the infection prevalence was 52.94% (27/51) and 71.64% (48/67) in spring and summer, respectively. Gastrointestinal parasites are a serious problem in cattle and buffaloes in the lower district of Dir Khyber Pakhtunkhwa Pakistan. In general, the burden of parasitic infection was low in most animals that received previous anti-parasitic treatment.

CEBPß binding directly to the promoter region drives CEBPɑ transcription and improves FABP4 transcriptional activity in adipose tissue of yak (Bos grunniens).

Fatty acid binding protein 4 (FABP4) was crucial to fatty acid uptake and intracellular transport. However, the mechanisms regulating yak (Bos grunniens) FABP4 transcription were not determined. In the current study, predominant expression levels of yak FABP4 were identified in subcutaneous fat and longissimus dorsi muscles by quantitative real-time polymerase chain reactions (qPCR). The CCAAT/enhancer binding protein alpha (CEBPα) and myocyte enhancer factor 2A (MEF2A), as transcriptional activator or repressor in the promoter region of FABP4, were confirmed by both site-directed mutagenesis experiment and chromatin immunoprecipitation assay. Additionally, molecular mechanisms of CEBPɑ regulation were analyzed to explore the transcriptional regulatory property of FABP4, which indicated that transcriptional activity of CEBPɑ depended on CCAAT/ enhancer binding protein beta (CEBPß) transcription factor. Our results demonstrated that CEBPß binding directly to the promoter region drove CEBPɑ transcription, improving yak FABP4 transcriptional activity in adipocytes. This mechanism expanded the information on the transcriptional regulatory network of adipogenesis.