Curative Agent Research Articles

The alleviative efficacy of sildenafil and chrysin against zinc oxide nanoparticles-provoked hepatic and blood toxicity: role of MyD88/NF-κB1/TNF-α pathway

BackgroundZinc oxide nanoparticles are nanoparticles of metal oxide with semiconductor properties and proved many noxious effects on the mammalian cell. Sildenafil, a phosphodiesterase inhibitor, and chrysin, one of the flavonoids, proved to have anti-inflammatory and anti-oxidative stress effects.Methods48 rats were grouped into 8 groups equally. 1. (Control group) received normal diet and NaOH was added to water, 2. (chrysin group): 250 mg/kg, orally for 10 days, 3. (sildenafil group): 40 mg/kg, orally for 14 days, 4. (ZnO-NPs group): 200 mg/kg, intraperitoneal for 10 days, 5. (ZnO-NPs + chrysin as a prophylactic agent): given in the same previous doses and durations consecutively, 6. (ZnO-NPs + chrysin as a curative agent): given in the same previous doses and durations with chrysin given after ZnO-NPs administration for 10 days, 7. (ZnO-NPs + sildenafil as a curative agent): given in the same previous doses and durations with sildenafil given after ZnO-NPs administration for 10 days, and 8. (Combined treatment group chrysin + sildenafil) as combined treatment were given in the same previous doses and durations after ZnO-NPs administration for 10 days. Blood and samples from tissues were withdrawn for histopathological, biochemical studies, and comet assay at the end of the experiment.ResultsSildenafil and chrysin proved to protect from hepatotoxicity and hematotoxicity induced by zinc oxide nanoparticles as they lessened aspartate transaminase, alanine transferase, and alkaline phosphatase levels. They also reduced the oxidative stress enzyme levels. Gene expression of myeloid differentiation factor 88, nuclear factor kappa B1, tumor necrosis factor, and DNA damage decreased with treatment. Also, there was an improvement in the histopathological picture of the liver seen with treatment. Concurrent administration of sildenafil and chrysin revealed much better improvement than either drug used alone.ConclusionChrysin and sildenafil have ameliorative effects against ZnO-NPs-induced hepatotoxicity and hematotoxicity, their protective effect is either preventive with chrysin or curative with chrysin and sildenafil.

Therapeutic potential of kaempferide against paraquat instigated cardiac toxicity in rats

Paraquat (PQ) is an effective herbicide however, due to its adverse effects on different organs including heart, it is considered as highly toxic to human beings. Kaempferide (KMF) is a plant-based flavonoid with conspicuous pharmacological properties. This experiment was executed to evaluate the palliative actions of KMF on PQ prompted cardiac toxicity in rats. Twenty-four rats were apportioned into 4 equal groups which were designated as control, toxicant (PQ treated), Co-treated (PQ + KMF) and KMF group. After 30 days of treatment, PQ intoxication resulted in a remarkable reduction in antioxidant enzymes activities which include, glutathione reductase (GSH), glutathione S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione disulfide reductase (GSR), whereas an elevation was observed in reactive oxygen species (ROS), & malondialdehyde (MDA) as well as hydrogen peroxide (H2O2) level. Furthermore, concentrations of cardiac injury markers, creatinine phosphokinase (CPK), creatine kinase-myoglobin binding (CK-MB), & lactate dehydrogenase (LDH), as well as troponin I were increased in response to PQ treatment. Moreover, inflammatory cytokines such as tumour necrosis factor alpha (TNF-α), nuclear factor-kappa B (NF-κB), and interleukin-6 (IL-6), interleukin-1 beta (lL-1β), and cyclooxygenase-2 (COX-2) levels were augmented in PQ intoxicated group. PQ exposure reduced the gene expression of cardiac anti-apoptotic markers (Bcl-2), but the gene expression of apoptotic marker (caspase-9, caspase-3 and Bax) was increased. Histopathological damages were also observed in toxicant (PQ) exposed group. However, the administration of KMF significantly palliated PQ induced aforementioned disruptions. In the light of these findings, it is concluded that KMF is a promising bioactive compound that may be used as a curative agent against PQ instigated cardiac damage due to its marvelous antioxidant, anti-apoptotic, anti-inflammatory as well as cardioprotective potential.

Green Medicine for Weight Management: Medicinal Plants as promising curative agents in the treatment of Obesity

Obesity has become a global health crisis with substantial implications for public health. In the past 50 years, significant advancements have been made in the treatment of disorders like hypertension, adult-onset diabetes, and increased cholesterol that are directly related to obesity. However, the disease of obesity has proven to be mostly resistant to treatments, and anti-obesity drugs (AOMs) frequently have questionable safety and poor efficacy. Here, we give a summary of the history of AOM development with an emphasis on the lessons learned and current challenges. The search for next-generation AOMs that look capable of safely accomplishing significant and sustained body weight loss is motivated by recent developments, including improved knowledge of the molecular gut-brain communication. The exploration of medicinal plants for their anti-obesity potential has gained momentum due to their perceived safety and cultural acceptance.

Annickia affinis (Exell) Versteegh & Sosef methanol stem bark extract, potent fractions and isolated Berberine alkaloid target both blood and liver stages of malaria parasites

Ethnopharmacological relevanceHaving identified Annickia affinis as the most potent antiplasmodial plant constituent in a hepta-herbal Agbo-iba (HHA) formula commonly used to manage malaria in Benin city, Nigeria, we have in this study attempted to identify the specialized metabolites responsible for antiplasmodial activity of A. affinis through anti-blood stage malaria parasite activity guided isolation of potent molecules from its stem bark methanol extract. After that, phenotypic effects, including stage-specific kill kinetics, were investigated. Further, the crude extract, its potent fractions, and specialized metabolites were also tested against the liver-stage malaria parasite. Materials and methodsA. affinis was subjected to molecular PCR-based analysis to confirm its identity. Thereafter, extraction of its stem bark with methanol was carried out. Alkaloid enriched fractions from this stem bark extract were obtained using the acid-base-solvent extraction method. These alkaloid-enriched fractions were subjected to various chromatographic techniques that led to the isolation of two protoberberine alkaloids identified as berberine and palmatine based on NMR and mass spectrometry analysis. The efficacy of crude extract, fractions and purified alkaloids was tested against the malaria parasite's blood and liver stages, respectively. Results and DiscussionAnnickia affinis methanol extract, fractions, and the isolated protoberberine alkaloids showed excellent antiplasmodial activity with good selectivity against blood-stage malaria parasite. Thus, their IC50 against various strains of the parasite ranged from 0.95 to 18.65 μg/ml, while CC50 against Human embryonic kidney (HEK) and the human hepatoma (HUH-7) cell lines ranged between 10 and > 100 μg/ml. Interestingly, the crude extract and the alkaloid enriched fractions showed promising activity against the liver-stage malaria parasite. Between berberine and palmatine isolated from the potent fractions, only the former showed ∼100% and 90% inhibitions of liver stage parasite at 5 μg/ml and 1 μg/ml, respectively, while the latter showed no inhibition even at 20 μg/ml. ConclusionThis study reports that the ethnomedicinal use of HHA to manage malaria can be attributed to the presence of promising antiplasmodial protoberberine alkaloids together with synergistic effects via either enhancement of bioavailability or improved pharmacokinetics by other phytoconstituent(s) coming from other HHA constituent plants. The protoberberine alkaloids isolated have been identified as fast-acting antiplasmodial agents, with activity against all erythrocytic stages of the malaria parasite. Further, A. affinis methanol stembark extract and the protoberberine alkaloid berberine isolated from it also displayed excellent activity (>90% inhibition at 1 μg/ml) against the liver-stage malaria parasite. A. affinis and HHA can thus be useful as both liver-stage prophylactic and blood-stage curative agents.

Treatment with biological products for chronic urticaria

Background: Chronic urticaria is characterized by repeatedly occurring itchy wheals and/or angioedema for at least six weeks. The prevalence of chronic urticaria is increasing globally, with variations observed among different regions. Chronic urticaria has a long duration and may recur over time. Effective and tolerable treatment for such patients is crucial due to unpredictable, recurrent, and disabling symptoms, as well as the significant impact on quality of life.Current Concepts: Recent guidelines recommend the regular use of non-sedative second generation antihistamines as the first line of treatment for chronic urticaria. For patients whose urticarial symptoms persist or worsen with the approved dose of antihistamines, the guideline recommends the second line of treatment, which involves either increasing the dosage of the initial antihistamine or combining it with three other kinds of antihistamines. However, almost half of patients with chronic urticaria are refractory to antihistamines. Recently, treatment modulating immunoglobulin E (IgE) levels and activities was found to provide an efficient therapeutic approach. Omalizumab, the only approved anti-IgE treatment to date for patients with chronic urticaria, has demonstrated strong evidence of both efficacy and safety. Recent international guidelines recommend omalizumab as the first choice of treatment for antihistamine-refractory chronic spontaneous urticaria.Discussion and Conclusion: As omalizumab is not a curative and disease-modifying agent, there is a subpopulation of patients with chronic spontaneous urticaria who partly or have never responded to omalizumab. To address this, ongoing research is exploring the therapeutic potential of other biological products that target various aspects, such as type 2 inflammation, complement system, and the c-kit pathway.

Drying temperature affects the hypolipidemic, antioxidant, and antihypertensive potential of Hibiscus sabdariffa calyx in rats induced with L-NAME

The effects of different drying temperatures on the hypolipidemic, antioxidant, and antihypertensive potential of Hibiscus sabdariffa calyx was evaluated. The calyx were dried under different temperature conditions (− 58 °C, 30 °C, 40 °C, and 50 °C), and extracted with a solvent mixture of ethanol and water (1:4 % w/v). To induce hypertension, the rats were administered with 40 mg/kg body weight dose of N-nitro L-arginine methyl-ester (L-NAME), via the intra-gastric route. H. sabdariffa extract was administered orally, at varying doses (250, 500, and 1000 mg/kg) to the rats. Afterwards, the hypolipidemic, antioxidant, and antihypertensive potentials of the extracts were evaluated using standard validated methods. Induction with L-NAME significantly (p < 0.05) increased the total cholesterol, triglyceride, and LDL levels, significantly decreased the HDL levels; significantly (p < 0.05) increased the levels of LPO/MDA, H2O2, and decreased GPx, and SOD activities; significantly (p < 0.05) increased the pressures (diastolic and systolic); significantly (p < 0.05) increased ACE and arginase activities, glucose level, and significantly decreased nitric oxide activity. Treatment with H. sabdariffa extract significantly (p < 0.05) reversed these trends in the hypertensive experimental rats. The hypolipidemic, antioxidant, and antihypertensive properties of the extract from the calyx of H. sabdariffa, which varies with the drying temperatures of the calyx, portends its potential as a curative agent in the treatment of hypertensive conditions, and other cardiovascular diseases.

Hepatoprotective effects of astragalin against polystyrene microplastics induced hepatic damage in male albino rats by modulating Nrf-2/Keap-1 pathway

The current study was designed to determine the curative potential of astragalin (AST) against polystyrene microplastics (PS-MPs) induced hepatic toxicity in rats. PS-MPs exposure decreased the expression of Nrf-2 and anti-oxidant enzymes, while increasing Keap-1 expression. The activities of glutathione-S-transferase, catalase, glutathione, glutathione peroxidase, superoxide dismutase, glutathione reductase and heme oxygenase-1 were decreased, besides the levels of malondialdehyde and reactive oxygen species were also increased following the exposure of PS-MPs. The intoxication of PS-MPs elevated aspartate aminotransferase, alanine transaminase, alkaline phosphatase levels, as well as cyclooxygenase-2 activity, interleukin-6, interleukin-1 beta, nuclear factor-kappa B and tumor necrosis factor-alpha levels were also escalated. Furthermore, Bcl-2 expression was down-regulated, while Bax and Caspase-3 expressions were upregulated following PS-MPs exposure. Histopathological assessment revealed substantial liver damages in PS-MPs treated rats. However, AST supplementation substantially recovered PS-MPs-induced damages and histological anomalies. Therefore, AST can be used as a curative agent to treat PS-MPs-prompted hepatotoxicity due to its anti-apoptotic, anti-inflammatory and anti-oxidant potentials.

An Ethnobotanical Survey on Medicinal Plants used to treat Urinary Tract Infections in Kanyakumari District

This study is an attempt made to explore the indigenous knowledge of medicinal flora used to treat urinary tract infections in Kanyakumari district, Tamil Nadu, India. The information was collected by intensively interviewing the indigenous people, experienced aged rural folks, traditional healers and herbal drug sellers of Kanyakumari district. A total of 29 medicinal plants belonging to 21 families were identified to be used as curative agents against urinary tract infections by dwellers of Kanyakumari district. The medicinal plants were arranged alphabetically based on its botanical name and other details such as local names in Tamil, family name, plant part used, method of preparation and route of administration were recorded. The indigenous knowledge obtained through this survey might aid the scientific community to investigate these plants for discovery of bioactive compounds that could serve as curative agents against urinary tract infections in future.

Identification of Phthalates, Methyl Esters and Siloxanes through GCMS analysis, biological investigation, DFT and Molecular Docking studies on Methanolic Subfractions of Hibiscus Rosa Sinensis flower extract

Purpose: Plants are vital source of bioactive molecules, so they play a significant role in prevention and curing of various health disorders. The Hibiscus rosa sinensis, an ornate with attractive flowers, has conventionally been utilized globally as a curative agent for a wide range of ailments. Methods: In current study, we prepared crude methanolic extract of flowers of Hibiscus rosa sinensis and subjected that to in vitro biological evaluation to assess its antidiabetic and antioxidant potential. Outcomes of in vitro evaluation confirmed the excellent antidiabetic and antioxidant potency of Hibiscus flowers. Further crude methanolic extract was fractionated to hexane, ethyl acetate and methanol fractions. Among the three fractions, we subjected methanolic fraction to GCMS analysis to explore the bioactive molecules contained by this fraction. Results: The spectral data obtained from GCMS analysis revealed the existence of a total of 12 compounds including phthalates, methyl esters and siloxanes which are known to have a range of reported pharmacological activities. Successively, we subjected the identified molecules to molecular docking to assess their antidiabetic and antioxidant potential and DFT study to explore the reactivity of their molecular structures. As far as we are aware, it is the first report on the in-silico antidiabetic (128.1µM) and antioxidant (410.0µM) potential assessment of phytoconstituents of methanolic extract of floral part of Hibiscus rosa sinensis. The results revealed the H. Sinensis plat as more viable and good alternative to existing natural remedies.

Host-Bacterium Interaction Mechanisms in Staphylococcus aureus Endocarditis: A Systematic Review.

Staphylococci sp. are the most commonly associated pathogens in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations, and the protracted infection courses, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid's version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. Thirty-five studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored, giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. The goal of this study is to attain a better understanding on the molecular pathways involved in infective endocarditis supported by S. aureus and whether therapeutic avenues for the prevention and treatment of IE can be obtained. The use of antibiotic-treated allogeneic tissues have marked antibacterial action, thereby becoming the ideal substitute in native and prosthetic valvular infections. However, the development of effective vaccines against S. aureus still requires in-depth studies.

In Vivo Anti-Diabetes Potential of Huntera Umbellata Seed

The possible use of ethanol extract of Hunteria umbellata seed as a curative agent in alloxan-induced diabetic rats was investigated. A total of forty-eight adult albino Wistar rats (male: weighed 150 g – 250 g; aged 16 – 19 weeks) were used for this study. Completely randomized design was used for this experiment. Standard methods were used to ascertain the blood glucose levels, kidney function test, serum lipid profile, and liver enzymes. Also, the radical scavenging activity was carried out using the DPPH (2,2-diphenyl-1-picyhydrazyl) method. The results showed that the administration of alloxan has led to significantly increased blood glucose levels in rats. The diabetic control group had constant high blood glucose level that was &gt;250 mg/dl, whereas a significant decrease in blood glucose level was witnessed when the rats were pre-treated with the seed extract. Again, the extract was found to reduce certain biochemical parameters such as overall cholesterol, triglyceride, low density lipoprotein, alanine aminotransferase, alkaline phosphatase, urea and creatinine. while high density lipoprotein was increased. Also, the radical scavenging activity (RSA) study revealed that the seed has inhibitory concentration (IC50) of 227.34 µg/ml as compared to the IC50 of superoxide dismutase (389.73 µg/ml).The observed effects of the extract could be possibly due to its ability to reduce oxidative damage to insulin-producing β-cell membranes, thus, resulting in increased insulin concentration and sensitivity in the cells. Therefore, in this study it was suggested that ethanol extracts of osu seeds could be a potential candidate for the management of diabetes due to its hypoglycaemic effects.

Biofabricated Palladium Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposite Using the Punica granatum (Pomegranate) Peel Extract: Investigation of Potent In Vivo Hepatoprotective Activity against Acetaminophen-Induced Liver Injury in Wistar Albino Rats.

Acute acetaminophen (APAP) toxicity is a predominant clinical problem, which causes serious liver injury in both humans and experimental animals. This study presents the histological and biochemical factor and antioxidant enzyme level changes induced by an acute acetaminophen overdose in Wistar albino rat livers to elucidate the effective hepatoprotective potential of biofabricated palladium nanoparticle-decorated reduced graphene oxide nanocomposites (rGO/PdNPs-NC) compared to silymarin. After detailed characterization of the hepatoprotective potential of the synthesized rGO/PdNPs-NC, the rats were divided into eight groups (n = 6): control group (normal saline, 1 mL/kg b.w.), silymarin, Punica granatum (pomegranate) peel extract, PdNPs, reduced graphene oxide (rGO-PG), and reduced graphene oxide palladium nanocomposites (rGO/PdNPs-NC, low and high doses) for 7 successive days. The acetaminophen (APAP)-treated group was administered a single dose of acetaminophen (2 g/kg b.w.) on the 8th day. The histopathological results showed that the acetaminophen overdose group exhibited massive intrahepatic hemorrhagic necrosis around the centrilobular region with hepatocytes with vacuolization and swollen cytoplasm found in the liver architecture. This hepatopotential was further assessed by various biochemical parameters such as SGOT, SGPT, ALB, ALP, LDH, direct bilirubin, total bilirubin, and total protein. Also, the antioxidant parameters such as SOD, CAT, MDA, GSH, GRD, and GST were assayed. Rats of groups 7 and 8 showed a significant decrease in SGOT, SGPT, ALP, LDH, direct bilirubin, and total bilirubin (p < 0.001), while a significant increase in the final total protein and ALB as compared to group 2 rats (p < 0.001) was observed. The antioxidant parameters exhibited that rats of groups 7 and 8 showed a significant (p < 0.001) increase in the level of SOD, CAT, GSH, GRD, and GST without affecting the MDA as compared to group 2 rats. Also, the hepatoprotective potential of rGO/PdNPs-NC (low and high doses) was comparable to that of the standard reference drug silymarin. The present study reveals that the rGO/PdNPs-NC possesses significant hepatoprotective activity and acts as an effective and promising curative agent against acetaminophen-induced hepatotoxicity.

Clinical characteristics of blue rubber bleb nevus syndrome in adults: systematic scoping review

Background Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular anomaly mainly affecting the skin, central nervous system and gastrointestinal tracts. Its clinical presentation and characteristics in adult patients are unclear. Aim To clarify the characteristics of BRBNS in adult patients with a focus on gastrointestinal symptoms. Methods Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including ‘Blue rubber bleb nevus syndrome’ from their inception to 28 December 2021. Results Ninety-nine articles, including 3 observational studies and 101 cases from case reports and series, were included. Observational studies were consistently with small sample sizes, and there was only one prospective study to show the effectiveness of sirolimus in BRBNS. Common clinical presentations included anemia (50.5%) and melena (26.5%). While skin findings were known to be representative of BRBNS, only 57.4% had known vascular malformation. The diagnosis was primarily made clinically, with only 1% being diagnosed with BRBNS through genetic sequencing. Distribution of BRBNS-related lesions were variable, but predominantly oral (55.9%), followed by small bowel (49.5%), colorectal (35.6%) and stomach (26.7%) vascular malformations. Conclusion While it has been underrecognized, adult BRBNS could be a culprit for refractory microcytic anemia or occult gastrointestinal bleeding. Further studies are critical to establish a uniform understanding of diagnosis and treatment for those with adult BRBNS. The utility of genetic testing in adult BRBNS diagnosis and the patient characteristics that may benefit from sirolimus, a potentially curative agent, remain to be clarified.

Challenges in the Long-term Management of Patients With Coccidioidal Meningitis: A Retrospective Analysis of Treatment and Outcomes.

Coccidioidal meningitis (CM) is the most severe form of disseminated coccidioidomycosis. Despite years of clinical experience, it remains a difficult condition to treat, often requiring surgical procedures, such as placement of a ventriculoperitoneal shunt, in addition to lifelong antifungal therapy. We performed a retrospective analysis of patients with CM seen in a large referral center in Central Valley, California, from 2010 to 2020. Data pertinent to CM were collected and analyzed. Among 133 patients with CM identified in the 10-year period, nonadherence to antifungal therapy was noted in 43% of patients. Of the 80 patients who underwent ventriculoperitoneal shunt placement for management of intracranial pressure, shunt failure requiring revision surgery occurred in 42 (52.5%). Rehospitalizations due to CM-related reasons occurred in 78 of 133 patients (59%). Twenty-three percent of patients (n = 29) died due to complications from CM, on an average 22 months after the diagnosis of CM. Encephalopathy at presentation was associated with a significantly higher risk of death. Patients with CM in central California are predominantly rural agricultural workers with elevated levels of poverty and low health literacy and many barriers to care, leading to high rates of medication nonadherence and loss to follow-up outpatient care. Management challenges are frequent, such as failure of antifungal therapy, high rates of rehospitalization, and the need for repeated shunt revision surgeries. In addition to the development of curative new antifungal agents, understanding the barriers to patient adherence to care and antifungal therapy and identifying means to overcome such barriers are of paramount importance.

A delve into the pharmacological targets and biological mechanisms of Paederia foetida Linn.: a rather invaluable traditional medicinal plant.

Drug development from herbal medicines or botanical sources is believed to have a prominent role in the exploration of novel counteractive drugs that has sparked much interest in recent times. Paederia foetida is one such medicinal plant used in both traditional and folkloric medicine. Several parts of the herb are locally utilised as a natural curative agent for several ailments since time immemorial. Paederia foetida indeed possesses anti-diabetic, anti-hyperlipidaemic, antioxidant, nephro-protective, anti-inflammatory, antinociceptive, antitussive, thrombolytic, anti-diarrhoeal, sedative-anxiolytic, anti-ulcer, hepatoprotective activity, anthelmintic and anti-diarrhoeal activity. Furthermore, growing evidence shows many of its active constituents to be effective in cancer, inflammatory diseases, wound healing and spermatogenesis as well. These investigations shed light on possible pharmacological targets and attempts to establish a mechanism of action for these pharmacological effects. These findings contrast the significance of this medicinal plant for further research and for the exploration of novel counteractive drugs to establish a mechanism of action before being employed to healthcare. Pharmacological activities of Paederia foetida and their mechanism of action.

Effect of The Combination of Kefa Forest Honey and Euphorbia hirta as a Curative agent of Vibrio alginolyticus in the Hybrid Grouper Epinephelus fuscoguttatus

Kefa forest honey and Euphorbia hirta have an antibacterial effect against pathogenic bacteria in fish. This work investigated the combination of honey and E. hirta against Vibrio alginolitycus in the hybrid grouper Epinephelus fuscoguttatus. The active ingredients and antibacterial activity of Kefa forest honey and E. hirta were tested in vitro at different concentrations using the disk method. The experimental animals were injected with V. alginolitycus suspension at a concentration of 106 cells ml−1/fish. After the fish showed symptoms of infection, the treatment was carried out for 5 consecutive days by immersion in the mixture of 25% Kefa honey and E. hirta at different concentrations of honey and E. hirta combinations. After treatment, the fish were monitored for 7 days. During the study, observations on hematology and clinical symptoms were made. The results showed that the combination of Kefa honey and E. hirta had antibacterial activity against V. alginolitycus in vitro and in vivo can increase the hematological profile of grouper and alleviate clinical symptoms due to V. alginolitycus infection. The results showed that administration of a combination Kefa forest honey and E. hirta was effective as a cure for V. alginolyticus infection in grouper.

Isolation and evaluation of Bacillus subtilis RSS-1 as a potential biocontrol agent against Sclerotinia sclerotiorum on oilseed rape

Sclerotinia stem rot caused by Sclerotinia sclerotiorum is one of the most important diseases of oilseed rape in the world. Because of the absence of resistant varieties and the disadvantages of chemical control, application of antifungal microbes has become an eco-friendly and effective measure to control this disease. In this study, Bacillus subtilis strain RSS-1, isolated from soil samples, was identified based on morphological, physiological and biochemical tests, and DNA gyrase subunit A (gyrA), gyrB, DNA-directed RNA polymerase subunit beta (rpoB) and rpoC gene sequence analysis. It significantly inhibited mycelial growth and sclerotial production of S. sclerotiorum in vitro. In greenhouse experiments, all three tested concentrations (106, 107, 108 cfu mL−1) of cell fermentation broth and culture filtrate significantly reduced the severity of sclerotinia stem rot on oilseed rape (P < 0.05). RSS-1 was more effective at reducing disease severity when applied 24 h before inoculation with S. sclerotiorum than at 24 h post inoculation, suggesting that RSS-1 should be applied as a prophylactic rather than a curative biological agent. Colonization tests indicated that the population density of RSS-1 on rapeseed leaves significantly decreased (P < 0.05) over 6 days. However, RSS-1 could stably colonize in rhizospheric soil of rapeseed over 30 days. Challenge inoculation tests showed that RSS-1 significantly inhibited the activities of polygalacturonase and cellulase and accumulation of oxalic acid during the S. sclerotiorum infection. These results suggest that RSS-1 was a potential biological agent for controlling sclerotinia stem rot caused by S. sclerotiorum on oilseed rape.

Characterization and Biological Studies of Synthesized Titanium Dioxide Nanoparticles from Leaf Extract of Juniperus phoenicea (L.) Growing in Taif Region, Saudi Arabia

Green synthesis of metal nanoparticles in nanosized form has acquired great interest in the area of nanomedicine as an environmentally friendly and cost-effective alternative compared to other chemical and physical methods. This study deals with the eco-friendly green synthesis of titanium dioxide nanoparticles (TiO2 NPs) utilizing Juniperus phoenicea leaf extract and their characterization. The biosynthesis of TiO2 NPs was completed in 3 h and confirmed by UV-Vis spectroscopy, a strong band at 205.4 nm distinctly revealed the formation of NPs. Transmissions electron microscopy (TEM) analysis showed the synthesized TiO2 NPs are spherical in shape, with a diameter in a range of 10–30 nm. The XRD major peak at 27.1° congruent with the (110) lattice plane of tetragonal rutile TiO2 phase. Dynamic light scattering (DLS) analysis revealed synthesized TiO2 NPs average particle size (hydrodynamic diameter) of (74.8 ± 0.649) nm. Fourier transmission infrared (FTIR) revealed the bioactive components present in the leaf extract, which act as reducing and capping agents. The antimicrobial efficacy of synthesized TiO2NPs against, Staphylococcus aureus, and Bacillus subtilis (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), Yeast strain (Saccharomyces cerevisiae) and fungi (Aspergillus niger, and Penicillium digitatum) assayed by a disc diffusion method. TiO2NPs inhibited all tested strains by mean inhibition zone (MIZ), which ranged from the lowest 15.7 ± 0.45 mm against K. pneumoniae to the highest 30.3 ± 0.25 against Aspergillus niger. The lowest minimum inhibitory concentration (MIC) and bactericidal (MBC) values were 20 μL/mL and 40 μL/mL of TiO2NPs were observed against Asp. niger. Moreover, it showed significant inhibitory activity against human ovarian adenocarcinoma cells with IC50 = 50.13 ± 1.65 µg/mL. The findings concluded that biosynthesized TiO2 NPs using Juniperus phoenicea leaf extract can be used in medicine as curative agents according to their in vitro antibacterial, antifungal, and cytotoxic activities.

Prophage-Derived Regions in Curtobacterium Genomes: Good Things, Small Packages.

Curtobacterium is a genus of Gram-positive bacteria within the order Actinomycetales. Some Curtobacterium species (C. flaccumfaciens, C. plantarum) are harmful pathogens of agricultural crops such as soybean, dry beans, peas, sugar beet and beetroot, which occur throughout the world. Bacteriophages (bacterial viruses) are considered to be potential curative agents to control the spread of harmful bacteria. Temperate bacteriophages integrate their genomes into bacterial chromosomes (prophages), sometimes substantially influencing bacterial lifestyle and pathogenicity. About 200 publicly available genomes of Curtobacterium species, including environmental metagenomic sequences, were inspected for the presence of sequences of possible prophage origin using bioinformatic methods. The comparison of the search results with several ubiquitous bacterial groups showed the relatively low level of the presence of prophage traces in Curtobacterium genomes. Genomic and phylogenetic analyses were undertaken for the evaluation of the evolutionary and taxonomic positioning of predicted prophages. The analyses indicated the relatedness of Curtobacterium prophage-derived sequences with temperate actinophages of siphoviral morphology. In most cases, the predicted prophages can represent novel phage taxa not described previously. One of the predicted temperate phages was induced from the Curtobacterium genome. Bioinformatic analysis of the modelled proteins encoded in prophage-derived regions led to the discovery of some 100 putative glycopolymer-degrading enzymes that contained enzymatic domains with predicted cell-wall- and cell-envelope-degrading activity; these included glycosidases and peptidases. These proteins can be considered for the experimental design of new antibacterials against Curtobacterium phytopathogens.

A Semi-mechanistic Model to Characterize the Long-Term Dynamics of Hepatitis B Virus Markers During Treatment With Lamivudine and Pegylated Interferon.

Antiviral treatments against hepatitis B virus (HBV) suppress viral replication but do not eradicate the virus, and need therefore to be taken lifelong to avoid relapse. Mathematical models can be useful to support the development of curative anti-HBV agents; however, they mostly focus on short-term HBV DNA data and neglect the complex host-pathogen interaction. This work aimed to characterize the effect of treatment with lamivudine and/or pegylated interferon (Peg-IFN) in 1,300 patients (hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative) treated for 1 year. A mathematical model was developed incorporating two populations of infected cells, namely , with a high transcriptional activity, that progressively evolve into , at a rate , representing cells with integrated HBV DNA that have a lower transcriptional activity. Parameters of the model were estimated in patients treated with lamivudine or Peg-IFN alone (N=894), and the model was then validated in patients treated with lamivudine plus Peg-IFN (N=436) to predict the virological response after a year of combination treatment. Lamivudine had a larger effect in blocking viral production than Peg-IFN (99.4-99.9% vs. 91.8-95.1%); however, Peg-IFN had a significant immunomodulatory effect, leading to an enhancement of the loss rates of (×1.7 in HBeAg-positive patients), (> ×7 irrespective of HBeAg status), and (×4.6 and ×2.0 in HBeAg-positive and HBeAg-negative patients, respectively). Using this model, we were able to describe the synergy of the different effects occurring during treatment with combination and predicted an effect of 99.99% on blocking viral production. This framework can therefore support the optimization of combination therapy with new anti-HBV agents.