Ameliorative impacts of interleukin 35 or thymoquinone nanoparticles on lipopolysaccharide-induced renal injury in rats.

Interleukin-35 (IL-35) is a novel anti-inflammatory component, and its role in protecting against acute kidney disease (AKD) has not been explored. Thymoquinone (TQ) has been widely used for many therapeutic targets. Inflammation/oxidative signaling plays essential roles in the pathogenesis of diverse disorders, such as AKD, cancer, cardiac disease, aging, and metabolic and neurodegenerative disorders. The objective of the investigation was to evaluate how IL-35 prevents inflammation and oxidative stress indicators in the kidneys of rats caused by lipopolysaccharide (LPS). The experimental rats were allocated into six groups: control (0.5 mL saline); TQ (0.5 mg/kg, b.w. IP), IL-35 (100 µg of IL-35 /kg, b.w. IP), LPS (500 µg/kg b.w. IP), LPS + IL-35, and LPS + TQ. Results indicate that the hematological and blood biochemical parameters were substantially restored by TQ or IL-35 therapy. The elevation of kidney function (uric acid, creatinine, and cystatin C) and oxidative related biomarkers (MDA, PC, and MYO) in rat kidneys was significantly restored by the TQ and IL-35 therapies after LPS administration (P < 0.05). Serum immunological variables IgM and IgG were significantly restored by TQ and IL-35 in LPS-treated rats. Both IL-35 and TQ markedly mitigated the decrease antioxidant related biomarkers (SOD, GSH, CAT and TAC) triggered by LPS. The IL-35 and TQ treatments significantly diminished serum levels of inflammatory responses such as TNF-α, NF-κB, IL-6 and IFN-γ, and significantly increased IL-10 in LPS-treated rats. Additionally, serum levels of MCP, Caspase-3, andBcl-2 were significantly diminished by TQ or IL-35 therapy. The histopathology and immunohistochemistry for NF-kB, PCNA and TNF-α cytokines revealedremodeling when treated with TQ and IL-35. In summary, administration of IL-35 or TQ can attenuateLPS-induced renal damage by extenuatingoxidative stress, tissue impairment, apoptosis, and inflammation, implicating IL-35 as a promising therapeutic agent in acute-related renal injury.

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.

Immunomodulatory, Antioxidant, and Anti-Inflammatory Activities of Green Synthesized Copper Nanoparticles for Treatment of Chronic Toxoplasma gondii Infection.

BACKGROUND: Nowadays, interest in the use of nanotechnology for medical purposes is increasing. The current experimental investigation is planned for the green synthesis, characterization, and efficacy of copper nanoparticles (CLN) against chronic Toxoplasma gondii infection. METHODS: Green synthesis of CNP was performed using the Lupinus arcticus extract via the precipitation method. The effects of CNP on tachyzoites, infectivity rate, parasites inside THP-1 cells, nitric oxide (NO) triggering, iNOS, and IFN-γ expression genes were evaluated. Following toxoplasmosis in BALB/c mice via the T. gondii ME49 strain, mice received CNP at 5 and 10 mg/kg/day alone and combined with pyrimethamine (PYM) at 5 mg/kg for two weeks. CNP's in vivo effects were evaluated by analyzing the load and size of cysts, oxidant/antioxidant enzymes, and bradyzoite surface antigen 1 (BAG1) expression gene levels. RESULTS: CNP displayed a circular shape ranging from 10 to 85 nm. The IC50 value of CNP and PYM against tachyzoites was 37.2 and 25.7 µg/mL, respectively, whereas the CC50 value of CNP and pyrimethamine against THP-1 cells was 491.4 µg/mL and 269.5 µg/mL, respectively. The rate of infectivity and parasite load among THP-1 cells exposed to CNP was obviously reduced (p < 0.05). CNP at the doses of 5 and 10 mg/kg predominantly along with PYM evidently (p < 0.05) reduced the number and size of the T. gondii cysts in the infected mice. The levels of NO, iNOS, and IFN-γ genes were remarkably (p < 0.001) boosted compared with the cells without treatment. CNP at the doses of 10 and 20 mg/kg drastically (p < 0.05) reduced the oxidative stress markers in the infected mice, whereas CNP significantly elevated the level of antioxidant factors. CNP also revealed no toxicity in the liver and kidney at the tested doses in healthy mice. CONCLUSIONS: Our experimental study reported the beneficial effects of CNP principally along with existing chemical drugs against latent toxoplasmosis in mice, whereas the possible action mechanisms of CNP are controlling oxidative stress, refining antioxidant enzymes, and increasing the production of immunomodulatory cytokines with no toxicity to the function of vital organs. But, additional trials are required to confirm these results, as well as to clarify the accurate mechanisms and their toxicity.

Potent In Vitro and In Vivo Effects of Stachys lavandulifolia Methanolic Extract against Toxoplasma gondii Infection.

The present study aimed to evaluate the in vitro, in vivo, and safety of Stachys lavandulifolia Vahl. methanolic extract (SLME) against acute toxoplasmosis caused by Toxoplasma gondii RH strain in mice. METHODS: MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the in vitro effect of the SLME on T. gondii tachyzoites. Totally, 72 male BALB/c mice (40 mice for in vivo evaluation of SLME and 32 mice for its toxicity effects on liver and kidney serum enzymes) were used for the present investigation. At first, 40 mice were orally pre-treated with the SLME at doses of 25, 50, and 75 mg/kg/day for two weeks. Mice were checked daily, and the rate of survival and the mean number of tachyzoites were recorded. Liver lipid peroxidation (LPO) and nitric oxide (NO) levels, the effects on kidney and liver function, as well as the expression level of the proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ), were studied by the quantitative real-time PCR. Flow cytometry analysis was performed on the effects of SLME on the detection of apoptotic and necrotic cells in T. gondii tachyzoites. RESULTS: The SLME at the concentrations 75 and 150 µg/mL completely killed the tachyzoites after 2 hr of incubation. SLME at 25, 50, and 75 mg/kg/day increased the survival rate of infected mice by the sixth, seventh, and eighth days, respectively. SLME also significantly (p < 0.05) decreased the LPO and NO levels and upregulated the IL-1ß and IFN-γ mRNA gene expression levels, whereas no considerable change was observed in the serum level of kidney and liver enzymes. Flow cytometry analysis revealed the prompted early and late apoptosis after exposure to T. gondii tachyzoites with various concentrations of SLME. CONCLUSION: We found the relevant in vitro anti-Toxoplasma effects of SLME against T. gondii. Moreover, the results confirmed the promising in vivo prophylactic effects of SLME. SLME provokes the innate immune system, induces apoptosis, modulates the proinflammatory cytokines, and inhibits hepatic injury in infected mice. With all these descriptions, further surveys are required to support these findings and elucidate this plant's possible mechanisms of action.

Anti-Cancer Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) and Its Cellular Mechanisms against Human Hepatoma Cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common form of liver cancer that occurs in hepatocytes. Although many chemical drugs, e.g., cisplatin, methotrexate, taxis, and doxorubicin are used to treat HCC, there have been numerous reports related to the side effects of these drugs (e.g., emerging drug resistance, bone marrow failure, and gastrointestinal disorders). These issues led scientists to search for the novel anti-cancer drugs, mainly in natural products with greater efficiency and less toxicity. The current survey was intended to assess the anti-cancer effects of queen bee acid (10-Hydroxy-2-Decenoic Acid, 10-HDA) and its cellular mechanisms against the human hepatoma cell line HepG2. MATERIALS AND METHODS: The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to evaluate the effect of 10-HDA on the viability of HepG2 cells. The initial and late apoptosis in the HepG2 cells treated with 10-HDA were assessed by the Annexin-V (AV) assay. The level of the gene and protein expression of some apoptosis genes (e.g., caspase-3, Bcl-2-associated X protein (BAX), and B-cell lymphoma protein 2 (Bcl-2)), Poly (ADP-ribose) polymerases (PARP), and miRNA-34a (miR-34a), were measured by real-time PCR and Western blot. RESULTS: The obtained findings revealed that HepG2 cell viability was markedly reduced (p < 0.01) following exposure to 10-HDA in a dose-dependent matter. The calculated half maximal cytotoxic concentration (CC50) value of 10-HDA was 59.6 µg/mL for HepG2 cells, while this value for normal THLE-3 cells was 106.4 µg/mL. We found that 10-HDA markedly elevated (p < 0.01) the percentage of necrotic and apoptotic cells from 0.94 to 9.7 and 27.6%, respectively. The real-time PCR results showed that the expression levels of the caspase-3, Bax, and miR-34a genes were significantly (p < 0.001) elevated. Contrary to these results, a significant (p < 0.01) reduction in the expression level of the Bcl2 gene was observed. The levels of protein expression of Caspase-3, PARP, and Bax were markedly elevated following exposure of HepG2 cells to 10-HDA at » CC50, ½ CC50, and CC50. The level of protein expression of Bcl-2 was markedly reduced following exposure of HepG2 cells to 10-HDA at » CC50, ½ CC50, and CC50 (p < 0.01). CONCLUSION: The current results confirmed the potent in vitro cytotoxic effects of 10-HDA on HepG2 cells with no significant cytotoxic effects on normal cells. Although its mechanisms of action have not been fully studied, the induction of apoptosis via different pathways was determined as one of the principle mechanisms of action of 10-HDA against HepG2 cells. Nevertheless, additional surveys must be performed to clearly understand the mechanisms of action and safety of this fatty acid.

Molecular Interactions of Zyesami with the SARS-CoV-2 nsp10/nsp16 Protein Complex.

BACKGROUND: SARS-CoV-2 emerged in late 2019 and caused COVID-19. Patients treated with Zyesami were found to have a 3-fold decrease in respiratory failure and improved clinical outcomes. It was reported that Zyesami inhibits RNA replication of SARS-CoV-2, including several non-structural proteins essential in viral RNA replication. SARS-CoV-2 is a distinctive virus that requires nsp10 and nsp16 for its methyltransferases activity which is crucial for RNA stability and protein synthesis. OBJECTIVE: We aimed the in silico determination of inhibitory consequences of Zyesami on the SARS-CoV-2 nsp10/nsp16 complex. Targeting SARS-CoV-2 nsp10/ nsp16 protein complex may be used to develop a drug against COVID-19. METHODS: I-TASSER was used for secondary structure prediction of Zyesami. CABS-dock was used to model Zyesami with SARS-CoV-2 nsp16 interaction. The docked complex was visualized using PyMol. The quality of the docking model was checked by using ProQdock. RESULTS: The 3D structure of SARS-CoV 2, nsp10/nsp16 showed that essential interactions exist between nsp10 and nsp16. Significant contact areas of Zyesami exist across amino acid residues of nsp10; Asn40-Thr47, Val57-Pro59, Gly69-Ser72, Cys77-Pro84, Lys93-Tyr96. In addition, polar contacts between nsp16 and Zyesami are Asn299-Ser440, Val297-Asn443, Gly149-Tyr437, Gln159-Lys430, Asn178- Arg429, Ser146-Arg429, Ser146-Arg429, Lys147-Arg429, Asr221-Thr422, Lys183-Asp423, Lys183-Asp423, and Gln219-Asp423 the residues are shown of nsp16 and Zyesami respectively. CONCLUSION: The structural bioinformatics analyses have indicated the potential binding specificity of Zyesami and nsp16. Data predict how the initial binding of Zyesami with nsp10 and nsp16 may occur. Moreover, this binding could significantly inhibit the 2 -O-MTase activity of the SARSCoV nsp10/16 complex.

Development of surface modified bilosomes for the oral delivery of quercetin: optimization, characterization in-vitro antioxidant, antimicrobial, and cytotoxicity study.

Quercetin (QT) is a flavonoid that exhibits anti-oxidant and chemo-preventive activity. This research work aimed to develop surface-modified bilosomes (BS) of QT. The BS was prepared by the solvent evaporation method and optimized by the Box-Behnken design. The optimized QT-BS (QT-BS3opt) displayed vesicle size (143.51 nm), PDI (0.256), zeta potential (-15.4 mV), and entrapment efficiency (89.52%). Further, the optimized QT-BS formulation was coated with chitosan (CS). The XRD diffractogram of CS-QT-BS3opt1 did not exhibit extensive peaks of QT, revealing that QT is properly encapsulated in the polymer matrix. The QT-BS3opt and CS-QT-BS3opt1 exhibited sustained-release (86.62 ± 3.23% and 69.32 ± 2.57%, respectively) up to 24 h with the Korsmeyer-Peppas kinetic model (R2 =0.9089). CS-QT-BS3opt1 exhibited significantly (P < .05) high flux, i.e. 4.20-fold more than pure QT dispersion and 1.27-fold higher than QT-BS3opt. CS-QT-BS3opt1 showed significantly greater bio-adhesion (76.43 ± 2.42%) than QT-BS3opt (20.82 ± 1.45%). The antioxidant activity showed that QT from CS-QT-BS3opt1 has more remarkable (P < .05) antioxidant activity at each concentration than pure QT. The CS-QT-BS3opt1 exhibited 1.61-fold higher cytotoxicity against MFC7 and 1.44-fold higher cytotoxicity against MDA-MB-231 than pure QT. The CS-QT-BS3opt1 displayed a significantly greater antimicrobial potential against E. coli than against S. aureus. From all these findings, it could be concluded that surface-modified QT-BS might be an effective approach for increasing the efficacy of QT in the treatment of certain ailments.

Biosynthesis and Characterization of Silver Nanoparticles Produced by Phormidium ambiguum and Desertifilum tharense Cyanobacteria.

The world faces a challenge with the pervasion of multidrug-resistant bacteria that encourages scientists to develop and discover alternative, ecofriendly, and easy-to-produce new antibacterial agents. Our work is part of the greater effort of scientists around the world to achieve this goal by the biological synthesis of silver nanoparticles using cyanobacterial extracellular and intracellular components as nonchemical reducing agents. Two Egyptian cyanobacteria were isolated and identified according to 16S rRNA gene sequencing as Phormidium ambiguum and a novel species Desertifilum tharense. The sequences were deposited with accession numbers MW762709 and MW762710 for Desertifilum tharense and Phormidium ambiguum, respectively, in the GenBank. The results of UV-Vis analysis showed promising extracellular Ag-NPs synthesis by Desertifilum tharense and Phormidium ambiguum under light conditions. Therefore, these Ag-NPs were characterized and evaluated for antibacterial and antioxidant activity. TEM and SEM analyses revealed the spherical crystals with face-centered cubic structures and size range of 6.24-11.4 nm and 6.46-12.2 nm for Ag-NPs of Desertifilum tharense and Phormidium ambiguum, respectively. XRD and EDX results confirmed the successful synthesis of Ag-NPs in their oxide form or chloride form. The FTIR spectrum data confirmed the presence of hydroxyl and amide groups. Desertifilum tharense Ag-NPs displayed the largest inhibition zone that ranged from 9 mm against Micrococcus luteus ATCC 10240 to 25 mm against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. For Phormidium ambiguum Ag-NPs, the inhibition zone diameter was in the range of 9 mm to 18 mm. The biosynthesized Ag-NPs significantly inhibited the growth of medically important resistance-pathogenic Gram-positive and Gram-negative bacteria. The Ag-NPs of Phormidium ambiguum exhibited the highest scavenging activity of 48.7% when compared with that of Desertifilum tharense, which displayed 43.753%.

10-Dehydrogingerdione Attenuates Tramadol-Induced Nephrotoxicity by Modulating Renal Oxidative Stress, Inflammation and Apoptosis in Experimental Rats: Role of HO-1 Activation and TLR4/NF-κB/ERK Inhibition.

Tramadol represents a synthetic opioid analgesic especially for mild to severe pain. Its dose must be commonly monitored according to pain status and to alleviate the appearance of any adverse effects such as renal cellular damage during its excretion. Present work aimed mainly to study the effects of tramadol intake on renal tissues and 10-dehydrogingerdione (10-DHGD) potential as a protective agent. Tramadol administration induced an increase in serum levels of urea, creatinine, uric acid, the renal immune expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and caspase-3 which turned out to be decreased by 10-DHGD intake. Our results also recorded a significant increase in renal malondialdehyde (MDA), toll-like receptor 4 (TLR4), and extracellular signal-regulated protein kinase-1 (ERK1) along with glutathione (GSH), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) decrease due to tramadol intake, which were counteracted by 10-DHGD administration as illustrated and supported by the histopathological findings. Our conclusion refers to renoprotective potential of 10-DHGD against tramadol adverse effects.

Preliminary Study of Gastroprotective Effect of Aloe perryi and Date Palm Extracts on Pyloric Ligation-Induced Gastric Ulcer in Experimental Rats.

OBJECTIVE: The present study was aimed at investigating the possible antiulcer activities of some natural phytochemicals Aloe perryi leaf extract (APLE) and flower extract (APFE) in addition to the date palm seed extract (DPSE) and the oily samples of DPSE in a pylorus ligation-induced ulcer model using ranitidine as a standard antiulcer drug. BACKGROUND: Peptic ulcer is a prevalent gastrointestinal disorder due to hypersecretion of gastric acid. It affects four million people worldwide, and 2-10% of these ulcers are perforated and cause bleeding. This increases the risk of morbidity and mortality. So we aimed to introduce a primary study alternatively safe method for treating peptic ulcer. MATERIALS AND METHODS: Forty-two Wistar Albino rats of either sex were randomly divided into seven groups (6/each). The pylorus ligation was done to induce ulcer in pretreated albino rats. The antiulcer activities of extracts were estimated at different dose levels (250 and 500 mg/kg) using ranitidine as a standard drug (50 mg/kg). Gastric volume, pH, and total and free acidity as well as ulcer index and percentage of ulcer inhibition were measured to elucidate the antiulcerogenic effects. Histological examination of gastric ulcer was also performed. Statistical analysis for the results was done where P < 0.05 was considered statistically significant. RESULTS: Pylorus ligation for 6 h in control rats resulted in gastric ulcer which was indicated by the accumulation of gastric secretion and increased total acidity and decreased pH. The pretreatment of rats with APLE, APFE, and DPSE in addition to the oily samples of DPSE significantly inhibited the ulcers induced by pylorus ligation. These effects were attributed to significant reductions in total and free acidity, ulcer index, and gastric volume while there is a marked decrease in gastric pH (the antisecretory) as well as mucosal strengthening properties of these phytochemicals. CONCLUSION: These findings give these extracts the potential to be a promising tool for the management of gastric ulcer after performing further clinical and experimental studies. Our study demonstrated the promising antiulcer activity of extracts and oils in pyloric ligation-induced gastric ulcer. To the best of our knowledge, this is the first study to explore the antiulcer activity of these extracts; however, further investigations may be recommended for full details about this antiulcerogenic capacity.

In vitro and in vivo Anti-Toxoplasma Effects of Allium sativum Essential Oil Against Toxoplasma gondii RH Strain.

BACKGROUND: Since no effective vaccine has been developed for toxoplasmosis, prophylaxis in seronegative pregnant women and immunocompromised patients with a CD4 <100 cells/µL is highly recommended as an ideal strategy to prevent this disease. This study aimed to assess the chemical composition, in vitro, and in vivo effects of Allium sativum essential oil (ASEO) against Toxoplasma gondii RH strain. METHODS: The in vitro anti-Toxoplasma effects of different concentrations of ASEO (32.5, 75, 150 µg/mL) were measured by MTT assay for 0.5, 1, 2, and 3 h. Male Balb/c mice were orally administrated ASEO at the doses of 200, 400, and 600 µg/kg/day for 14 days. One day after the completion of oral drug administration, the mice in all groups were infected intraperitoneally with 1×104 tachyzoites. They were checked daily and the rate of survival was recorded. The peritoneal fluids of the mice were collected and the mean number of tachyzoites was calculated via a light microscope. The level of liver lipid peroxidation (LPO) and nitric oxide (NO), toxicity effects on the liver and kidney, and the mRNA expression levels of some pro-inflammatory cytokines such as IL-1ß and IFN-γ were determined by quantitative real-time PCR. RESULTS: Different concentrations of ASEO showed a significant (p < 0.001) anti-Toxoplasma activity against T. gondii tachyzoites, and the highest efficacy was observed at the concentration of 150 µg/mL. Fourteen days of pre-treatment of infected mice with ASEO at the doses of 200, 400, and 600 µg/kg/day significantly (p < 0.001) decreased the mean number of tachyzoites and mortality rate by the 6th, 7th, and 8th days after infection, respectively. ASEO at the doses of 200, 400, and 600 µg/kg/day significantly (p < 0.05) improved the increase in the LPO and NO. Pre-treatment of mice with different doses of ASEO provoked a considerable (P < 0.001) downregulation of IL-1ß and IFN-γ mRNA gene expression levels, but it had no significant toxicity on the serum levels of some liver and kidney enzymes. CONCLUSION: The present study demonstrated the considerable prophylactic effects of ASEO that increased the survival rate of mice and reduced the parasite load in them. Our findings also showed that ASEO promotes the innate immune system, pro-inflammatory cytokines, inhibition of hepatic injury, etc. in the mice with acute toxoplasmosis. However, additional investigations are mandatory to clarify the accurate prophylactic and therapeutic anti-Toxoplasma mechanisms of ASEO as well as all its toxicity aspects, especially in clinical settings.

Nanoparticles as Alternatives for the Control of Haemonchus contortus: A Systematic Approach to Unveil New Anti-haemonchiasis Agents.

Haemonchus contortus is an infectious gastrointestinal nematode parasite of small ruminants. This study addresses the in vitro/in vivo anti-haemonchiasis potential, toxicological effects, and mechanism of action of nanoparticles. Online databases were used to search and retrieve the published literature (2000 to 2021). A total of 18 articles were selected and reviewed, out of which, 13 (72.2%) studies reported in vitro, 9 (50.0%) in vivo, and 4 (22.2%) both in vitro/in vivo efficacy of different nanoparticles. Mostly, organic nanoparticles (77.7%) were used including polymeric (85.7%) and lipid nanoparticles (14.3%). The highest efficacy, in vitro, of 100% resulted from using encapsulated bromelain against eggs, larvae, and adult worm mortality at 4, 2, and 1 mg/ml, respectively. While in vivo, encapsulated Eucalyptus staigeriana oil reduced worm burden by 83.75% and encapsulated Cymbopogon citratus nano-emulsion by 83.1%. Encapsulated bromelain, encapsulated Eucalyptus staigeriana oil, and encapsulated Cymbopogon citratus nano-emulsion were safe and non-toxic in vivo. Encapsulated bromelain damaged the cuticle, caused paralysis, and death. Nanoparticles could be a potential source for developing novel anthelmintic drugs to overcome the emerging issue of anthelmintic resistance in H. contortus. Studies on molecular effects, toxicological consequences, and different pharmacological targets of nanoparticles are required in future research.

Microbial aspects and potential markers for differentiation between bacterial and viral meningitis among adult patients.

OBJECTIVES: Meningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for differentiation between bacterial and viral meningitis. METHODOLOGY: Adult patients with acute meningitis were subjected to lumber puncture. Cerebrospinal fluid (CSF) microorganisms were identified using Real-time PCR. PCT and CRP levels, peripheral and CSF-leucocyte count, CSF-protein and CSF-glucose levels were assessed. RESULTS: Out of 80 patients, infectious meningitis was confirmed in 75 cases; 38 cases were bacterial meningitis, 34 cases were viral meningitis and three cases were mixed infection. Higher PCT, peripheral and CSF-leukocytosis, higher CSF-protein and lower CSF-glucose levels were more significant in bacterial than viral meningitis patients. Neisseria meningitides was the most frequent bacteria and varicella-zoster virus was the most common virus. Using ROC analyses, serum PCT and CSF-parameters can discriminate bacterial from viral meningitis. Combined ROC analyses of PCT and CSF-protein significantly improved the effectiveness in predicting bacterial meningitis (AUC of 0.998, 100%sensitivity and 97.1%specificity) than each parameter alone (AUC of 0.951 for PCT and 0.996 for CSF-protein). CONCLUSION: CSF-protein and serum PCT are considered as potential markers for differentiating bacterial from viral meningitis and their combination improved their predictive accuracy to bacterial meningitis.

Virus-receptor interactions of SARS-CoV-2 spikereceptor-binding domain and human neuropilin-1 b1 domain.

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wahan, China and it causes disease which is known as COVID-19. This infection spreads everywhere in the world, and it leads to an enormous number of death among individuals. The mystery issue about SARS-CoV-2 that appears not to have functions of a hemagglutinin and neuraminidase like other coronaviruses. Angiotensin-converting enzyme 2 (ACE2) is the main surface receptor for entering SARS-CoV-2 into the host cell. This entry process is mediated by binding the SARS-CoV-2 spike receptor-binding domain (RBD) to ACE2. Recently, researchers discover a new receptor responsible for the SARS-CoV-2 entry which is neuropilin-1 (NRP1). So, this work provides afford a knowledge of how the initial interaction between SARS-CoV-2 spike RBD and NRP1 b1 domain may occur. Understanding this interaction would be very necessary for drug design against SARS-CoV-2.