Formulation of Neem and Echinacea Gel for Oral Health Along With the Evaluation of Antimicrobial, Cytotoxic, Anti-inflammatory, and Free Radical Scavenging Activity: An In Vitro Study.

Background Herbs have been used in medical practice for centuries and continue to play a significant role in modern complementary and alternative medicine. Phytochemicals in these herbs possess strong antioxidant and anti-inflammatory properties, which are beneficial in targeting oral health issues, such as dental plaque, gingivitis, and oral microbial infections. As research progresses, the challenge remains to translate these natural compounds into safe, effective, and accessible treatments for a wide range of diseases. Aim The aim of this research was to formulate the neem and echinacea gel along with the evaluation of antimicrobial, anti-inflammatory, free-radical scavenging activity, and cytotoxic potential. Materials and methods The neem and echinacea gel was prepared using a concentrated powdered mixture of neem and echinacea (5 grams each) to which 100 ml of distilled water was added, and the mixture was boiled for 30 minutes at 60°C. The 10 ml concentrate was mixed with 20 ml of a carbopol and carboxymethyl cellulose (CMC) mixture and mixed thoroughly, which resulted in neem and echinacea gel. Then, the antimicrobial, anti-inflammatory, cytotoxic potential, and free-radical scavenging activity of the gel were evaluated. The data obtained were statistically analyzed with the help of a paired t-test, where a p-value of less than 0.05 was considered statistically significant. Results The antimicrobial assay showed that neem and echinacea gel at the concentration of 100 micrograms showed a greater zone of inhibition against Staphylococcus aureus (3.15 ± 0.26), Streptococcus mutans (2.48 ± 0.45), Enterococcus faecalis (2.89 ± 0.15), and Candida albicans (4.28 ± 0.87). The cytotoxic test revealed that even at an 80 µg concentration of the extract, more than 70% of the nauplii were vital, which indicated that the gel was not cytotoxic. The highest anti-inflammatory activity (78.39 ± 1.82) of the gel was seen at 50 micrograms when compared with diclofenac sodium (73.16 ± 1.80). The free radical scavenging activity showed that the 2,2-diphenyl-1-picrylhydrazyl (DPPH) absorbance of the neem and echinacea extract was highest at 50 micrograms.  Conclusion The combination of neem and echinacea extract-based gel possessed high antimicrobial and anti-inflammatory activity when compared with standard drugs, such as amoxicillin and diclofenac sodium. The antioxidant activity of the gel was equal to butylated hydroxytoluene (BHT), and also the gel has a low cytotoxic potential even at its higher concentrations. Hence, the gel can be used as a natural remedy with minimal side effects, making it a valuable alternative to chemical agents.

Rapid detection of bactericidal efficacy of nanoparticles coated polyurethane foam by synchronous fluorescence spectroscopy.

The ability of right-angled synchronous fluorescence spectroscopy (SFS) was explored to analyse the bacterial load in water treated with green synthesized silver nanoparticles (AgNPs) coated polyurethane foam (PUF). Gram negative (Escherichia coli, Pseudomonas aeruginosa) and Gram positive (Staphylococcus aureus) bacteria cultured in nutrient broth were diluted in autoclaved water containing NPs-coated PUF. The survival rate of S. aureus and E. coli lowered after ten minutes as compared to P. aeruginosa; however, after thirty minutes, the percentage viability dropped and recorded as 3.4%, 0.9%, and 0.1% for E. coli, P. aeruginosa and S. aureus respectively in the treated suspensions. No spectral change was observed in the fluorescence emission from the positive control and treated bacterial suspension owing to the masking effect of the emission from nutrient broth. In parallel, SF spectra recorded for directly picked bacterial colony dissolved in water showed remarkable drop in tryptophan emission after treatment with NPs-coated PUF. The SF data changes were assisted by hierarchical cluster analysis, which also made it possible to distinguish between positive control and treated bacterial suspensions. SFS has shown to be a reliable substitute for the culture plate approach for the quick identification of bacterial contamination in water.

Biosynthesis of zinc oxide nanoparticles via neem extract and their anticancer and antibacterial activities.

In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-Vis), and dynamic light scattering (DLS). Then compare its efficacy as anticancer and antibacterial agents with chemically synthesized ZnO-NPs and the neem leaf extract used for the green synthesis of ZnO-NPs. The TEM, UV-vis, and particle size confirmed that the developed ZnO-NPs are nanoscale. The chemically and greenly synthesized ZnO-NPs showed their optical absorbance at 328 nm and 380 nm, respectively, and were observed as spherical particles with a size of about 85 nm and 62.5 nm, respectively. HPLC and GC-MS were utilized to identify the bioactive components in the neem leaf aqueous extract employed for the eco-friendly production of ZnO-NPs. The HPLC analysis revealed that the aqueous extract of neem leaf contains 19 phenolic component fractions. The GC-MS analysis revealed the existence of 21 bioactive compounds. The antiproliferative effect of green ZnO-NPs was observed at different concentrations (31.25 µg/mL-1000 µg/mL) on Hct 116 and A 549 cancer cells, with an IC50 value of 111 µg/mL for A 549 and 118 µg/mL for Hct 116. On the other hand, the antibacterial activity against gram-positive and gram-negative bacteria was estimated. The antibacterial result showed that the MIC of green synthesized ZnO-NPs against gram-positive and gram-negative bacteria were 5, and 1 µg/mL. Hence, they could be utilized as effective antibacterial and antiproliferative agents.

Anticoccidial potentials of Azadirachta indica ethosomal nanovesicle in broiler chicks.

This study evaluated the efficacy of Azadirachta indica ethosomal nanovesicle against Eimeria tenella infection in broiler chicks. Azadirachta indica ethanolic extract was screened phtochemically and analyzed active components of the extracts using high­performance liquid chromatography (HPLC). Azadirachta indica ethosomal nanovesicle was synthesized and characterized by zeta potential and scanning electron microscope. Broiler chicks were allocated into seven groups. Control group. The second group administered nanosized ethosomal vesicles (1 mL/kg b.wt.). The third group administered Azadirachta indica nanovesicles (30 mg/kg b.wt.) from 10th day of age. Fourth group was infected with E. tenella at a dose of 1 mL containing 40000 oocyst/ chick at 14th day of age. The fifth group administered Azadirachta indica nanovesicle (30 mg/kg b.wt.) from 10th day of age and infected with E. tenella as fourth group. The sixth group infected with E. tenella as the fourth group and treated with Azadirachta indica nanovesicle (30 mg/kg b.wt. for 4 days after clinical signs appearance. The seventh group infected with E. tenella as the fourth group and treated with diclazuril group (1 mL/4 L of water) for 2 successive days. Coccidiosis significantly decreased body weight, feed intake, reduced glutathione (GSH) level while increased feed conversion ratio, oocyst count, malonaldehyde (MDA) and nitric oxide (NO) serum levels, protein expression of interleukin-1 beta (IL-1ß), interleukin 6 (IL-6), BAX and Caspase 3, in cecal tissue and induced cecal tissue injury. However, administration of coccidiosis chicks Azadirachta indica nanovesicle enhanced body weight, and serum GSH. While decreased feed intake, feed conversion ratio, oocyst count, MDA, and NO serum levels, and protein expression of IL-1ß, IL-6, BAX, and caspase 3 in cecal tissues and ameliorated cecal tissue damage. This study indicated that, A. indica ethosomal nanovesicle had potent anticoccidial properties.

The Influence of Citrus Pectin and Polyacrylamide Modified with Plant-Derived Additives on the Properties of α-TCP-Based Bone Cements.

Materials based on highly reactive α-tricalcium phosphate (α-TCP) powder were developed and evaluated. Furthermore, the impact of different polymeric additives, such as citrus pectin or polyacrylamide (PAAM) modified with sago starch, neem flower, or rambutan peel, on the physiochemical and biological properties of the developed materials was assessed. The addition of modified PAAM shortened the setting process of bone cements and decreased their compressive strength. On the other hand, the addition of citrus pectin significantly enhanced the mechanical strength of the material from 4.46 to 7.15 MPa. The improved mechanical properties of the bone cement containing citrus pectin were attributed to the better homogenization of cementitious pastes and pectin cross-linking by Ca2+ ions. In vitro tests performed on L929 cells showed that 10% extracts from α-TCP cements modified with pectin are more cytocompatible than control cements without any additives. Cements containing PAAM with plant-derived modifiers show some degree of cytotoxicity for the highly concentrated 10% extracts, but for diluted extracts, cytotoxicity was reduced, as shown by a resazurin reduction test and live/dead staining. All the developed bone substitutes exhibited in vitro bioactivity, making them promising candidates for further biological studies. This research underscores the advantageous properties of the obtained biomaterials and paves the way for subsequent more advanced in vitro and in vivo investigations.

Antifungal Activity of Neem Leaf Extract With Eucalyptus citriodora Oil and Cymbopogon martini Oil Against Tinea Capitis: An In-Vitro Evaluation.

Introduction Tinea capitis, often known as ringworm of the scalp, is a fungal infection that affects the scalp, eyelashes, and eyebrows. It is generally caused by dermatophytes from the genera Trichophyton and Microsporum. Trichophyton tonsurans and Microsporum canis are the main etiological agents responsible for most of the cases of tinea capitis globally. Tinea capitis commonly manifests as itchy, scaly patches of hair loss. Tinea capitis is the prevailing dermatophyte illness among children globally. Methods An in-vitroevaluation study was conducted to assess the antifungal properties of ethanolic extracts of neem leaves and the oils of Eucalyptus citriodora and Cymbopogon martini, both individually and in combination. The agar-well diffusion method and the M38-A2 microbroth dilution method were employed to evaluate the antifungal efficacy against pathogenic dermatophyte strains, namely Microsporum canis and Trichophyton tonsurans. The fully mature green leaves were treated with ethanol to make the neem leaf extract. Additionally, high-performance liquid chromatographic analysis was carried out to determine the contents of the terpenoids. Fluconazole, an antifungal drug, is used as a standard. Results The findings demonstrated an overall inhibition of the growth of dermatophytes at a minimal inhibitory concentration of 187.5 and 375 µg/ml for neem leaf extract and 0.625 to 2.5 µl/ml for selected herbal oils, whereas it was 0.25 µg/ml and 0.50 µg/ml for positive control against Microsporum canis and Trichophyton tonsurans, respectively. Conclusion The phytochemical investigation of the ethanolic extracts in neem leaves revealed the presence of terpenoids, which are known for their significant biological activity. The study's findings demonstrated the therapeutic capabilities of neem leaf extract in combination with the oils of Eucalyptus citriodora and Cymbopogon martini for managing the tinea capitis infection. A broader and improved antifungal spectrum was seen when neem leaf extract and oils were combined. Therefore, it can be developed into a suitable formulation for the management of tinea capitis.

Addressing Challenges in Standardizing Helicobacter pylori Treatment Protocols: Importance and Review.

Helicobacter pylori, one of the top carcinogens, is associated with most cases of gastric cancer-related deaths worldwide. Over the past two decades, the rising rates of antibiotic resistance in the bacterium have reduced the efficacy of conventional antibiotic-based treatments. This underscores the urgency for continued research and novel treatment approaches. Establishing a worldwide accepted physician guideline for antibiotic prescription is crucial to combat antibiotic resistance and improve H. pylori infection management. Therefore, it is important to address the challenges that complicate the establishment of a universally accepted treatment protocol to prescribe an antibiotic regimen to eradicate H. pylori. The answers to the questions of why conventional standard triple therapy remains a first-line treatment choice despite its low efficacy, and how different factors affect therapy choice, are needed to identify these challenges. Hence, this review addresses concerns related to H. pylori treatment choice, role of antibiotic resistance and patient compliance in treatment outcomes, first-line vs. second-line therapy options, and methods for enhancing existing treatment methods. We also present a chart to aid antibiotic treatment prescription, which may support physician guidelines in this aspect. Eradication of H. pylori and patient adherence is paramount in overcoming antibiotic resistance in the bacterium, and our chart summarizes key considerations and suggests novel approaches to achieve this goal.

Effect of neem oil biodiesel on the surface and structural integrity of carbon steel alloy: Chromatographic, spectroscopic, and morphological investigations.

This study explores the impacts of neem oil biodiesel (BD), which was produced and characterized using GC-MS, FTIR, and UV-Vis spectroscopic techniques to elucidate pure and corrosion-product neem oil BD at room temperature (25 °C) and different immersion durations of 0, 28, 42, and 56 days. The OM and SEM were also employed to study the surface, structural integrity, and interphase interaction between the BD and the carbon steel (C1020) before and after immersion for different durations. The dominant fatty acid (FA) group in both pure and corrosion-product neem oil BD was C18, with a total composition of 72.3 %, hence determining the nature of the BD interaction with the carbon steel. The study revealed that carbon steel (C1020) was susceptible to attacks by neem oil BD, and the duration of immersion had substantial influence on the surface morphology and structural integrity of the steel. It is therefore anticipated that this study will significantly advance the field of alternative fuel research.

Synergistic antimicrobial action of chitosan-neem extracts nanoformulation as a promising strategy for overcoming multi-drug resistant bacteria.

The objective of the present study was to analyze and identify the phytochemical components found in neem leaf extracts using gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR) methods. The extract samples were acquired using ethyl acetate (EA) and petroleum ether (PE) solvents. Moreover, the extracts were assessed for their antibacterial and antioxidant features. In addition, chitosan nanoparticles (Cs NPs) containing neem extracts were synthesized and evaluated for their potential antibacterial properties, explicitly targeting multi-drug resistant (MDR) bacteria. The neem extracts were analyzed using GC-MS, which identified components such as hydrocarbons, phenolic compounds, terpenoids, alkaloids, and glycosides. Results revealed that the PE extract showed significant antibacterial activity against a range of bacteria. In addition, the PE extract exhibited significant antioxidant activity, exceeding both the EA extract and vitamin C. In addition, both extracts exhibited notable antibiofilm activity, significantly inhibiting the production of biofilm. The Cs NPs, loaded with neem extracts, exhibited significant antibacterial action against multidrug-resistant (MDR) microorganisms. The Cs NPs/EA materials had the greatest zone of inhibition values of 24 ± 2.95 mm against Pseudomonas aeruginosa. Similarly, the Cs NPs/PE materials exhibited a zone of inhibition measurement of 22 ± 3.14 mm against P. aeruginosa. This work highlights the various biochemical components of neem extracts, their strong abilities to combat bacteria and oxidative stress, and the possibility of Cs NPs containing neem extracts as effective treatments for antibiotic-resistant bacterial strains.

Feasibility Insights of the Green-Assisted Calcium-Phosphate Coating on Biodegradable Zinc Alloys for Biomedical Application: In Vitro and In Vivo Studies.

In the field of bone tissue engineering, recently developed Zn alloy scaffolds are considered potential candidates for biodegradable implants for bone regeneration and defect reconstruction. However, the clinical success of these alloys is limited due to their insufficient surface bioactivities. Further, the higher concentration of Zn2+ produced during degradation promotes antibacterial activity, but deteriorates osteogenic properties. This study fabricated an Azadirachta indica (neem)-assisted brushite-hydroxyapatite (HAp) coating on the recently developed Zn-2Cu-0.5Mg alloy to tackle the above dilemma. The microstructure, degradation behavior, antibacterial activity, and hemocompatibility, along with in vitro and in vivo cytocompatibility of the coated alloys, are systematically investigated. Microstructural analysis reveals flower-like morphology with uniformly grown flakes for neem-assisted deposition. The neem-assisted deposition significantly improves the adhesion strength from 12.7 to 18.8 MPa, enhancing the mechanical integrity. The potentiodynamic polarization study shows that the neem-assisted deposition decreases the degradation rate, with the lowest degradation rate of 0.027 mm/yr for the ZHN2 sample. In addition, the biomineralization process shows the apatite formation on the deposited coating after 21 days of immersion. In vitro cytotoxicity assay exhibits the maximum cell viability of 117% for neem-assisted coated alloy in 30% extract after 5d and the improved cytocompatibility which is due to the controlled release of Zn2+ ions. Meanwhile, neem-assisted coated alloy increases the ZOI by 32 and 24% for Gram-positive and Gram-negative bacteria, respectively. Acceptable hemolysis (<5%) and anticoagulation parameters demonstrate a promising hemocompatibility of the coated alloy. In vivo implantation illustrates a slight inflammatory response and vascularization after 2 weeks of subcutaneous implantation, and neo-bone formation in the defect areas of the rat femur. Micro-CT and histology studies demonstrate better osseointegration with satisfactory biosafety response for the neem-assisted coated alloy as compared to that without neem-assisted deposition. Hence, this neem-assisted brushite-Hap coating strategy elucidates a new perspective on the surface modification of biodegradable implants for the treatment of bone defects.

Biocompatible neem gum-modified polyvinyl alcohol composite as dielectric material for flexible energy devices.

In our pursuit of a flexible energy storage solution, we have developed biocompatible (bc)-NG/PVA composite polymers by combining neem tree gum (NG) with polyvinyl alcohol (PVA). This innovative bio-inspired approach harnesses NG's unique properties for both the bio-electrolyte and bio-electrode components. The resulting bc-NG/PVA composites exhibit superior dielectric strength and versatility, surpassing traditional inorganic ceramic dielectrics in advanced electronics and pulsed power systems. Our study investigates the dielectric characteristics, conductivities, electric modulus, and impedance parameters of Pure PVA and NG-doped PVA composites. Adding 5 % NG to PVA significantly boosts its conductivity from 10-8 S cm-1 to 10-4 S cm-1, while the dielectric constant of PVA/5 % NG composite jumps to 104.5 compared to pure PVA. These improvements position the composite films of 5 % NG added PVA as promising materials for diverse applications. The heightened performance of these NG-blended PVA composite materials underscores their potential as a valuable resource for flexible energy storage solutions.

Rosemary and neem: an insight into their combined anti-dandruff and anti-hair loss efficacy.

Dandruff, a common scalp disorder characterized by flaking dead skin, is often treated with conventional topical products. However, limitations exist due to potential side effects and high costs. Therefore, searching for natural, cost-effective solutions for dandruff and hair loss is crucial. Rosemary herb and neem tree, both cultivated in Egypt, possess well-documented anti-inflammatory properties derived from their rich phenolic phytoconstituents. This study formulated a standardized combined extract of rosemary and neem (RN-E 2:1) into hair gel and leave-in tonic formats. This extract demonstrated superior efficacy against Malassezia furfur (a causative agent of dandruff) and Trichophyton rubrum (associated with scalp disorders) compared to the conventional antifungal agent, ketoconazole. The combined extract (RN-E 2:1) also exhibited potent anti-inflammatory activity. Additionally, the suppression of iNOS expression is considered concentration-dependent. Quality control verified formulation stability, and ex-vivo studies confirmed effective ingredient penetration into the epidermis, the primary site of fungal presence. Remarkably, both formulations outperformed the standard treatment, minoxidil in hair growth trials. These findings highlight the potential of natural extracts for scalp and hair health.

The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study.

Introduction: Murine tumor growth restriction by neem leaf glycoprotein (NLGP) was established in various transplanted models of murine sarcoma, melanoma and carcinoma. However, the role of NLGP in the sequential carcinogenic steps has not been explored. Thus, tongue carcinogenesis in Swiss mice was induced by 4-nitroquinoline-1-oxide (4NQO), which has close resemblance to human carcinogenesis process. Interventional role of NLGP in initiation-promotion protocol established during 4NQO mediated tongue carcinogenesis in relation to systemic immune alteration and epithelial-mesenchymal transition (EMT) is investigated. Methods: 4NQO was painted on tongue of Swiss mice every third day at a dose of 25µl of 5mg/ml stock solution. After five consecutive treatment with 4NQO (starting Day7), one group of mice was treated with NLGP (s.c., 25µg/mice/week), keeping a group as PBS control. Mice were sacrificed in different time-intervals to harvest tongues and studied using histology, immunohistochemistry, flow-cytometry and RT-PCR on different immune cells and EMT markers (e-cadherin, vimentin) to elucidate their phenotypic and secretory status. Results: Local administration of 4NQO for consecutive 300 days promotes significant alteration in tongue mucosa including erosion in papillae and migration of malignant epithelial cells to the underlying connective tissue stroma with the formation of cell nests (exophytic-hyperkeratosis with mild dysplasia). Therapeutic NLGP treatment delayed pre-neoplastic changes promoting normalization of mucosa by maintaining normal structure. Flow-cytometric evidences suggest that NLGP treatment upregulated CD8+, IFNγ+, granzyme B+, CD11c+ cells in comparison to 4NQO treated mice with a decrease in Ki67+ and CD4+FoxP3+ cells in NLGP treated cohort. RT-PCR demonstrated a marked reduction of MMP9, IL-6, IL-2, CD31 and an upregulation in CCR5 in tongues from 4NQO+NLGP treated mice in comparison to 4NQO treated group. Moreover, 4NQO mediated changes were associated with reduction of e-cadherin and simultaneous up-regulation of vimentin expression in epithelium that was partially reversed by NLGP. Discussion: Efficacy of NLGP was tested first time in sequential carcinogenesis model and proved effective in delaying the initial progression. NLGP normalizes type 1 immunity including activation of the CD8+T effector functions, reduction of regulatory T cell functions, along with changes in EMT to make the host systemically alert to combat the carcinogenic threat.

Comparative Evaluation of Antimicrobial Effectiveness and Compressive Strength in Neem and Lemongrass-Modified Glass Ionomer Cement: An In Vitro Study.

Background Glass ionomer cement (GIC) demonstrates biocompatibility and fluoride ion release, indicating their potential to inhibit a wide range of bacteria, although this remains uncertain. Lemongrass and neem are recognized for their potent antimicrobial activity against numerous pathogenic microorganisms. The objective of the study is to evaluate the antimicrobial effectiveness and compressive strength of GIC modified with neem and lemongrass. Methodology Lemongrass and neem were incorporated into conventional GIC at varying concentrations. Group I - neem-modified GIC (0.5%, 1%, 2%), group II - lemongrass-modified GIC (0.5%, 1%, 2%), and group III (non-modified GIC as a control group). The disk-shaped specimens were then compared to unmodified GIC (control). Antimicrobial effectiveness was assessed using the minimal inhibitory concentration (MIC) assay against Streptococcus mutans and Lactobacillus. Compressive strength was assessed using a Universal Testing Machine, with a crosshead speed set to 0.5 mm per minute. Statistical analysis was conducted with a significance level set at p < 0.05. Results Neem modification displayed superior antimicrobial effectiveness against both Streptococcus mutans and Lactobacillus at all concentrations when compared to the control, with 2% showing the least mean value of 0.262. In contrast, lemongrass modification exhibited a significant difference in effectiveness against Streptococcus mutans but no difference against Lactobacillus. Neem modification demonstrated superior performance compared to lemongrass (p < 0.05). Both modified groups showed no significant impact on compressive strength. Conclusions Neem-modified GIC demonstrated the highest antimicrobial efficacy against Streptococcus mutans and Lactobacillus without altering its compressive strength. This suggests its potential as a promising alternative material in restorative dentistry. Additional in vivo investigations are needed to assess the extended-term effectiveness of the material.

The Neem Limonoid Nimbolide Modulates Key Components of the DNA Damage Response Signalling in Cellular and Animal Models of Oral Squamous Cell Carcinoma

BACKGROUND: Deregulated DNA damage response (DDR) network is implicated in cancer progression and therapy resistance. OBJECTIVE: The present study was designed to investigate whether nimbolide, an anticancer neem limonoid, targets key components of the DDR signalling pathway in cellular and animal models of oral squamous cell carcinoma (OSCC). METHODS: OSCC cells (SCC-4 and SCC-9), 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinoma model, chemoresistant OSCC patient-derived xenograft (PDX) model established in athymic nude mice, and tissue sections from patients with oral premalignant/malignant disease were used for the study. Key molecules that orchestrate the DDR, including the MRN complex, ATM, DNA-PKcs, H2AX, and p53, were analysed by qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry. Cell proliferation and apoptosis indices were evaluated. RESULTS: Nimbolide significantly reduced 8-oxodG levels, expression of MRN, ATMS1891, and γ-H2AX, with an increase in p-p53S15 in OSCC cells as well as in the HBP model. Nimbolide potentiated the effect of KU-55933 in ATM inhibition. In the PDX model, nimbolide suppressed tumor formation, stimulated DDR and apoptosis, inhibited cell proliferation, and enhanced sensitivity to cisplatin. Analysis of p-ATM expression revealed a significant increase during the sequential progression of hamster and human OSCC. CONCLUSIONS: This study provides compelling evidence that nimbolide functions as a DDR inhibitor in cellular and hamster OSCC models and as a DDR activator in the PDX model primarily by targeting ATM. Small molecules like nimbolide that modulate DDR are of immense benefit in cancer therapy. The study has also unveiled p-ATM as a promising biomarker of tumour progression in human OSCCs.

Immunological studies on the effects of toltrazuril and neem extract in broiler chickens suffering from coccidiosis.

Background: The prevalence of avian coccidiosis in the poultry industry has grown, resulting in substantial financial losses from high mortality, stunted growth, reduced productivity, and expensive medical expenses. Aim: The purpose of the current study was to assess the immunological effects of neem leaf extract and toltrazuril on broilers that had contracted coccidiosis. Methods: In this investigation, 100 one-day-old Cobb broiler chicks without sexes were employed. The chicks were divided into five equal groups, with 20 birds in each. On the 14th day of life, the birds in groups 2, 3, 4, and 5 received an oral inoculation with 1 × 105 sporulated oocysts of Eimeria tenella (E. tenella) (field isolate). The first group (Gp), which consists of 20 healthy broilers, served as a negative control. Gp (2) contains experimentally infected broilers and nontreated (served as a positive control). Gp (3) contains experimentally infected broilers treated with toltrazuril (1 ml/l drinking water) for two consecutive days. Gp (4) contains experimentally infected broilers treated with neem leaf extract 4% (50 ml/l drinking water) for 5 successive days, and Gp (5) contains experimentally infected broilers treated with toltrazuril (1 ml/l drinking water) and a half dose of neem leaves extract 4% (25 ml/l drinking water) for 5 successive days. For the purpose of estimating body weight growth and feed conversion ratio, each broiler was weighed separately at the start of the trial and again on the 1st and 10th day after treatment. In addition to obtaining intestinal samples for immunohistochemistry, blood samples were also obtained for immunological examination. Results: As compared to the negative control group, the experimentally infested broilers with E. tenella showed significant decreases in serum nitric oxide, lysosome, phagocytic percent, and phagocytic index, along with significant increases in white blood cells (WBCs), lymphocyte, heterophilis, eosinophilis, basophilis, monocyte, serum total protein, γ globulin, fibrinogen, and haptoglobin. When compared to the control positive group, experimentally infested broilers treated with either neem or toltrazuril alone or in combination demonstrated significant increases in serum total protein, nitric oxide, lysozyme, phagocytic percent, and phagocytic index, but significant decreases in WBCs, lymphocytes, heterophile, eosinophile, basophile, and monocyte. The intestinal peroxidase stain of broilers infected with E. tenella exhibited a significant positive expression for CD4, but the infected broilers treated with toltrazuril and half a dosage of neem displayed a negative expression for CD4, identical to the negative control. Conclusion: The broiler chickens infested with E. tenella may have a variety of negative impacts on their immune systems and immunohistopathological findings. Nonetheless, toltrazuril and neem extract, either separately or in combination, function as anticoccidial medications that may enhance the broiler chicks' immune state.

Antimicrobial efficacy of two commercially available herbal products with and without ultrasonic activation in primary endodontic infections: A randomized clinical trial.

Background: Effective irrigation is crucial for successful endodontic treatment. Traditional irrigants like sodium hypochlorite (NaOCl) have been widely used, but there is a growing interest in exploring natural alternatives for their potential antimicrobial properties. Objective: The study aims to compare the antimicrobial efficacy of Neem, Bitter Gourd, and NaOCl, with and without ultrasonic activation in managing primary endodontic infections. Materials and Methods: Ninety patients were randomly assigned six groups (n = 15) Group 1: NaOCl, Group 2: NaOCl with passive ultrasonic irrigation (PUI), Group 3: Neem juice, Group 4: Neem juice with PUI, Group 5: Bitter gourd juice, and Group 6: Bitter gourd juice with PUI. Bacteriological samples were collected before (S1) and after (S2) shaping, plated on brain heart infusion agar, and colony counting was done after 24 h. Statistical Analysis Used: Shapiro-Wilk test, one-way ANOVA, post hoc Tukey analysis, and paired t-test. Results: All the groups demonstrated a significant reduction in bacterial count. Groups with PUI (2, 4, 6) demonstrated higher mean bacterial reduction than their counterparts without PUI (1, 3, 5). Conclusion: Neem and Bitter gourd juices, particularly when used with PUI, demonstrated antimicrobial efficacy comparable to NaOCl with PUI.

Effect of nanoformulation Azadirachta indica on some factors associated with the vectorial capacity and competence of Anopheles aquasalis experimentally infected with Plasmodium vivax.

Malaria remains a highly prevalent infectious disease worldwide, particularly in tropical and subtropical regions. Effectively controlling of mosquitoes transmitting of Plasmodium spp. is crucial in to control this disease. A promising strategy involves utilizing plant-derived products, such as the Neem tree (Azadirachta indica), known for its secondary metabolites with biological activity against various insect groups of agricultural and public health importance. This study investigated the effects of a nanoformulation prototype Neem on factors linked to the vector competence of Anopheles aquasalis, a malaria vector in Latin America. Different concentrations of the nanoformulation were supplied through sugar solution and blood feeding, assessing impacts on longevity, fecundity, fertility, and transgenerational survival from larvae to adults. Additionally, the effects of the Neem nanoformulation and NeemAZAL® formulation on the sporogonic cycle of P. vivax were evaluated. Overall, significant impacts were observed at 100 ppm and 1,000 ppm concentrations on adult survival patterns and on survival of the F1 generation. A trend of reduced oviposition and hatching rates was also noted in nanoformulation-consuming groups, with fertility and fecundity declining proportionally to the concentration. Additionally, a significant decrease in the infection rate and intensity of P. vivax was observed in the 1,000 ppm group, with a mean of 3 oocysts per female compared to the control's 27 oocysts per female. In the commercial formulation, the highest tested concentration of 3 ppm yielded 5.36 oocysts per female. Concerning sporozoite numbers, there was a reduction of 52 % and 87 % at the highest concentrations compared to the control group. In conclusion, these findings suggest that the A. indica nanoformulation is a potential as a tool for malaria control through reduction in the vector longevity and reproductive capacity, possibly leading to decreased vector population densities. Moreover, the nanoformulation interfered with the sporogonic development of P. vivax. However, further basic research on Neem formulations, their effects, and mechanisms of action is imperative to gain a more specific perspective for safe field implementation.

Interactions between Bacillus thuringiensis and selected plant extracts for sustainable management of Phthorimaea absoluta.

Phthorimaea absoluta is a global constraint to tomato production and can cause up to 100% yield loss. Farmers heavily rely on synthetic pesticides to manage this pest. However, these pesticides are detrimental to human, animal, and environmental health. Therefore, exploring eco-friendly, sustainable Integrated Pest Management approaches, including biopesticides as potential alternatives, is of paramount importance. In this context, the present study (i) evaluated the efficacy of 10 Bacillus thuringiensis isolates, neem, garlic, and fenugreek; (ii) assessed the interactions between the most potent plant extracts and B. thuringiensis isolates, and (iii) evaluated the gut microbial diversity due to the treatments for the development of novel formulations against P. absoluta. Neem recorded the highest mortality of 93.79 ± 3.12% with an LT50 value of 1.21 ± 0.24 days, Bt HD263 induced 91.3 ± 3.68% mortality with LT50 of 2.63 ± 0.11 days, compared to both Bt 43 and fenugreek that caused < 50% mortality. Larval mortality was further enhanced to 99 ± 1.04% when Bt HD263 and neem were combined. Furthermore, the microbiome analyses showed that Klebsiella, Escherichia and Enterobacter had the highest abundance in all treatments with Klebsiella being the most abundant. In addition, a shift in the abundance of the bacterial genera due to the treatments was observed. Our findings showed that neem, garlic, and Bt HD263 could effectively control P. absoluta and be integrated into IPM programs after validation by field efficacy trials.

Neem leaf glycoprotein binding to Dectin-1 receptors on dendritic cell induces type-1 immunity through CARD9 mediated intracellular signal to NFκB.

BACKGROUND: A water-soluble ingredient of mature leaves of the tropical mahogany 'Neem' (Azadirachta indica), was identified as glycoprotein, thus being named as 'Neem Leaf Glycoprotein' (NLGP). This non-toxic leaf-component regressed cancerous murine tumors (melanoma, carcinoma, sarcoma) recurrently in different experimental circumstances by boosting prime antitumor immune attributes. Such antitumor immunomodulation, aid cytotoxic T cell (Tc)-based annihilation of tumor cells. This study focused on identifying and characterizing the signaling gateway that initiate this systemic immunomodulation. In search of this gateway, antigen-presenting cells (APCs) were explored, which activate and induce the cytotoxic thrust in Tc cells. METHODS: Six glycoprotein-binding C-type lectins found on APCs, namely, MBR, Dectin-1, Dectin-2, DC-SIGN, DEC205 and DNGR-1 were screened on bone marrow-derived dendritic cells from C57BL/6 J mice. Fluorescence microscopy, RT-PCR, flow cytometry and ELISA revealed Dectin-1 as the NLGP-binding receptor, followed by verifications through RNAi. Following detection of ß-Glucans in NLGP, their interactions with Dectin-1 were explored in silico. Roles of second messengers and transcription factors in the downstream signal were studied by co-immunoprecipitation, western blotting, and chromatin-immunoprecipitation. Intracellularization of FITC-coupled NLGP was observed by processing confocal micrographs of DCs. RESULTS: Considering extents of hindrance in NLGP-driven transcription rates of the cytokines IL-10 and IL-12p35 by receptor-neutralization, Dectin-1 receptors on dendritic cells were found to bind NLGP through the ligand's peripheral ß-Glucan chains. The resulting signal phosphorylates PKCδ, forming a trimolecular complex of CARD9, Bcl10 and MALT1, which in turn activates the canonical NFκB-pathway of transcription-regulation. Consequently, the NFκB-heterodimer p65:p50 enhances Il12a transcription and the p50:p50 homodimer represses Il10 transcription, bringing about a cytokine-based systemic-bias towards type-1 immune environment. Further, NLGP gets engulfed within dendritic cells, possibly through endocytic activities of Dectin-1. CONCLUSION: NLGP's binding to Dectin-1 receptors on murine dendritic cells, followed by the intracellular signal, lead to NFκB-mediated contrasting regulation of cytokine-transcriptions, initiating a pro-inflammatory immunopolarization, which amplifies further by the responding immune cells including Tc cells, alongside their enhanced cytotoxicity. These insights into the initiation of mammalian systemic immunomodulation by NLGP at cellular and molecular levels, may help uncovering its mode of action as a novel immunomodulator against human cancers, following clinical trials.