Harnessing the potential of nanoengineered siRNAs carriers for target responsive glioma therapy: Recent progress and future opportunities.

Past scientific testimonials in the field of glioma research, the deadliest tumor among all brain cancer types with the life span of 10-15 months after diagnosis is considered as glioblastoma multiforme (GBM). Even though the availability of treatment options such as chemotherapy, radiotherapy, and surgery, are unable to completely cure GBM due to tumor microenvironment complexity, intrinsic cellular signalling, and genetic mutations which are involved in chemoresistance. The blood-brain barrier is accountable for restricting drugs entry at the tumor location and related biological challenges like endocytic degradation, short systemic circulation, and insufficient cellular penetration lead to tumor aggression and progression. The above stated challenges can be better mitigated by small interfering RNAs (siRNA) by knockdown genes responsible for tumor progression and resistance. However, siRNA encounters with challenges like inefficient cellular transfection, short circulation time, endogenous degradation, and off-target effects. The novel functionalized nanocarrier approach in conjunction with biological and chemical modification offers an intriguing potential to address challenges associated with the naked siRNA and efficiently silence STAT3, coffilin-1, EGFR, VEGF, SMO, MGMT, HAO-1, GPX-4, TfR, LDLR and galectin-1 genes in GBM tumor. This review highlights the nanoengineered siRNA carriers, their recent advancements, future perspectives, and strategies to overcome the systemic siRNA delivery challenges for glioma treatment.

Synthesis, characterization, and anti-inflammatory properties of novel ethyl 3-benzoyl-7-(trifluoromethyl)indolizine-1-carboxylate derivatives: In silico and in vitro analysis.

Series of 7-(Trifluoromethyl) substituted indolizine 4a-g was synthesized using the one-pot method. Spectroscopic techniques such as IR, 1H-NMR, 13C-NMR, and HRMS were used for the structure confirmation of newly synthesized compounds. These 4a-g compounds were tested for their anti-inflammatory activity. In this study, we identified novel indolizine derivative compounds 4a-g selectively targeting COX-2 enzyme, tumor necrosis factor-α (TNF-α) and, interleukin-6 (IL-6). The in silico docking studies of 4a-g showed that these compounds have a higher affinity for COX-2 enzyme, TNF- α, and IL-6. In silico ADME profile analysis predicts that these compounds have good gastrointestinal tract and blood-brain barrier absorption. In vitro studies showed that compound 4d significantly reduces the level of COX-2 enzymes as compared to indomethacin. Compounds 4e, 4f, and 4a were also found to significantly reduce the level of TNF-α, while compounds 4f, 4g, and 4d, showed a reduction in the level of IL-6 when compared to indomethacin. Compounds 4a, 4d, and 4f also reduces nitric oxide (NO) level, compared to indomethacin. Overall, the current study illustrates significant anti-inflammatory activities of these novel 7-(Trifluoromethyl) substituted indolizine derivatives.

State-of-the-art drug delivery system to target the lymphatics.

PRIMARY OBJECTIVE: The primary objective of the review is to assess the potential of lymphatic-targeted drug delivery systems, with a particular emphasis on their role in tumour therapy and vaccination efficacy. REASON FOR LYMPHATIC TARGETING: The lymphatic system's crucial functions in maintaining bodily equilibrium, regulating metabolism, and orchestrating immune responses make it an ideal target for drug delivery. Lymph nodes, being primary sites for tumour metastasis, underscore the importance of targeting the lymphatic system for effective treatment. OUTCOME: Nanotechnologies and innovative biomaterials have facilitated the development of lymphatic-targeted drug carriers, leveraging endogenous macromolecules to enhance drug delivery efficiency. Various systems such as liposomes, micelles, inorganic nanomaterials, hydrogels, and nano-capsules demonstrate significant potential for delivering drugs to the lymphatic system. CONCLUSION: Understanding the physiological functions of the lymphatic system and its involvement in diseases underscores the promise of targeted drug delivery in improving treatment outcomes. The strategic targeting of the lymphatic system presents opportunities to enhance patient prognosis and advance therapeutic interventions across various medical contexts, indicating the importance of ongoing research and development in this area.

Potential involvement of ferroptosis in BPA-induced neurotoxicity: An in vitro study.

BACKGROUND: Ferroptosis is a newly recognized cell death pathway having distinct characteristics compared to traditional cell death pathways such as apoptosis, necroptosis, or autophagy. However, the potential involvement of ferroptosis in bisphenol A (BPA)-induced neurotoxicity has not been well explored so far. In present study, we analyzed the relationship between ferroptosis and BPA-induced neurotoxicity. METHODS: In this study, a human neuroblastoma cell line, SH-SY5Y, was treated with BPA, ferrostatin-1 (FS-1, ferroptosis inhibitor) and RSL-3 (ferroptosis inducer). The cell viability was measured using MTT assay. Additionally, the levels of lipid peroxidation, total iron content, reactive oxygen species (ROS) generation, and nitrite content were measured to evaluate the key markers of ferroptosis. To further confirm the involvement of ferroptosis in BPA-induced neurotoxicity, other ferroptosis markers such as glutathione peroxidase (GPx) activity, total glutathione contents and antioxidant parameters were also evaluated. RESULTS: The cell viability of SH-SY5Y cells was down-regulated by BPA treatment in a concentration-dependent manner, the cell viability at 0.1 µM concentration was 97.63% whereas at highest BPA concentration i.e. 10 µM, the cell viability was 86.05% (p < 0.0001). Also the antioxidant parameters including catalase and superoxide dismutase activity of neuronal cells were down-regulated upon BPA exposure. However, the levels of lipid peroxidation, total iron, reactive oxygen species, and nitrite contents were increased in a concentration-dependent manner which could be rescued by FS-1 and exacerbated by RSL-3. The total iron in SH-SY5Y cells at 0.1 µM concentration was found to be 1.2 fold (p < 0.05) of control and at highest BPA concentration total iron was about 1.41 fold (p < 0.001) of control. CONCLUSIONS: The present study indicated that, ferroptosis plays an important role in the progression of BPA-induced neurotoxicity, and ferroptosis may become a novel target in the treatment of various neurological disorders.

Nile Blue: A Red-Emissive Fluorescent Dye That Displays Differential Self-Assembly and Binding to G-Quadruplexes.

Nile Blue (NB) is a red-emissive dye that is well-known for imaging and staining applications. In this work, we describe the interaction of NB with various types of G-quadruplexes belonging to different topologies, molecularities, and conformations. Using spectroscopic techniques, we have determined the preferential binding of NB to c-Myc G-quadruplex and the other aspects of its binding. Concentration- and temperature-dependent studies showed that NB exists in a dynamic equilibrium between monomeric and H-aggregated states, which could be modulated by the addition of external agents such as anionic surfactants. NB displayed differential self-assembly with different types of G-quadruplex and duplex DNAs modulating its dynamic equilibrium between the monomeric and H-aggregated states. Fluorescence-based displacement studies revealed a 1:1 binding stoichiometry upon interaction with c-Myc G-quadruplex and an association constant of Kapp = 6.7 × 106 M-1. Circular dichroism studies indicated that NB does not cause changes in the overall conformation of either G-quadruplexes or duplexes; however, it does indicate nucleic acid-dependent self-assembly at higher concentrations. Heat capacity measurement showed a more negative change when compared to that in DNA duplex, indicating more burial of the polar surface area by NB to the G-quadruplex host.

Frailty screening associates with hospitalization and decline in quality of life and functional status in older patients with inflammatory bowel disease.

BACKGROUND AND AIMS: To study frailty screening in association with hospitalization and decline in quality of life (QoL) and functional status in older patients with Inflammatory Bowel Diseases (IBD). METHODS: A prospective multicentre cohort study in IBD patients ≥65 years using frailty screening (G8 Questionnaire). Outcomes were all-cause, acute and IBD-related hospitalization, any infection, any malignancy, QoL (EQ5D-3L) and functional decline (Instrumental Activities of Daily Living, (IADL)) during 18 months follow-up. Confounders: age, IBD type, biochemical disease activity (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 µg/g), comorbidity (Charlson Comorbidity Index). RESULTS: Out of 405 patients, median age 70 years, 196 (48%) screened at risk for frailty. All-cause hospitalizations occurred 136 times in 96 patients (23.7%), acute hospitalizations 103 times in 74 (18.3%). Risk of frailty did not associate with all-cause (aHR 1.5, 95% CI 0.9-2.4), but did associate with acute hospitalizations (aHR 2.2, 95% CI 1.3-3.8). Infections occurred in 86 patients (21.2%) and were not associated with frailty. Decline in QoL was experienced by 108 (30.6%) patients, decline in functional status by 46 (13.3%). Frailty screening associated with decline in QoL (aOR 2.1, 95% CI 1.3-3.6) and functional status (aOR 3.7, 95% CI 1.7-8.1). CONCLUSIONS: Frailty screening associates with worse health outcomes in older patients with IBD. Further studies are needed to assess feasibility and effectiveness of implementation in routine care.

Isolation, purification and characterization of quercetin from Cucumis sativus peels; its antimicrobial, antioxidant and cytotoxicity evaluations.

The peels of C.sativus are produced in large quantities in food processing industries and as kitchen-waste, resulting into tremendous loss of valuable bioactive components. Considering this, the flavanoids from C.sativus peels (CSP) were isolated and characterized by the column chromatography, high-performance thin-layer chromatography (HPTLC), Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) methods. The antioxidant and antibacterial activity of CSP extract against Escherichia coli, Streptococcus mutans and Pseudomonas aeruginosa was assessed. Scanning electron microscopy (SEM) was also used to investigate the killing efficacy of CSP extract against selected bacterial strains. Cytotoxic activity of extract was analyzed on L929 (connective tissue, Mouse, Mus Muscular) cell lines to check their viability. According to the results, total flavanoid content in CSP extract was found as 55.3 ± 1.154 µg/g QE and the chromatographic and spectral data of the isolated compound was elucidated as quercetin-a flavanoid. The CSP extract has also found to give significant antioxidant activity for both DPPH (2, 2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assay. The CSP extract was found to inhibit growth of E. coli, P. aeruginosa and S. mutans by forming inhibitory zones of 11.36 ± 0.47, 6.7 ± 0.36 mm and 10.16 ± 0.11 mm, respectively. The SEM results also confirm the rupturing of cells or biofilms of bacterial cells as compare to control strains. Additionally, CSP extract was found to not inhibit the proliferation of L929 cells and more than 90% viability of cells was achieved. The present finding highlights the phytochemical profile and therapeutic applications of C.sativus peels.

Purification, molecular docking and in vivo analyses of novel angiotensin-converting enzyme inhibitory peptides from protein hydrolysate of moth bean (Vigna aconitifolia (Jacq.) Màrechal) seeds.

The moth bean is a high-protein food legume. Enzymatic hydrolysates of food proteins demostrate health benefits. Search for diet related food protein hydrolysates is therefore within the scope of functional foods. Present study asertains to produce, screen and identify natural ACE-I inhibitory peptides derived from moth bean seed protein hydrolysates. The extracted protein was hydrolysed using alcalase, chymotrypsin, flavourzyme, papain, pepsin and trypsin respectively. Alcalase achieved the greatest degree of hydrolysis and ACE inhibition. The highest ACE-I inhibitory activity was exhibited by the peptide with the lowest molecular weight i.e. <3 kDa (IC50 11.19 ± 0.15 µg/mL). This was further separated by FPLC, followed by mass spectrometry. Molecular docking analysis showed the peptides IAWDFR and ADLPGLK bind to active sites whereas DKPWWPK and AVIPNAPNLR to non-active sites of the ACE molecule. In vivo administration of MBP hydrolysate to dexamethasone-induced hypertensive rats reduced their systolic blood pressure (125 ± 0.76 mmHg) compared with positive control (155 ± 3.13 mmHg). Moth bean protein peptides exhibit functional nutraceutical properties with adequate antihypertensive activity.

Value added bioactive compounds from fruits & vegetables waste for assessing their antimicrobial activity.

Since ancient time, plants and there parts have been used widely against dreadful pathogens due to ability of killing microbes. Waste from fruits and vegetables are pulling in more interest in exploration due to their therapeutic properties such as anti-pathogenic activity. In the present study antimicrobial and cytotoxicity properties of herbal combination prepared from peels of Allium cepa, Cucumis sativus, Citrus reticulata, and Mangifera indica were investigated. The herbal combination was tested for broad spectrum antimicrobial activity against Streptococcus mutans, Bacillus licheniformis, Lactobacillus plantarum, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii. The presence of phytochemical markers such as phenolics and flavanoids were also investigated. The results revealed that the herbal combination exhibited antimicrobial activity against S. mutans, B. licheniformis, L. plantarum, E. coli and moderate against P. aeruginosa and C. freundii. The presence of phenolics (798 ± 1.52 µg/g) and flavanoids (355.3 ± 2.081 µg/g) was also detected. Also, the herbal combination contains flavanoids such as quercetin and rutin was confirmed with the help of column chromatography, high-performance liquid chromatography (HPLC), fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) analysis. The herbal combination helps in the proliferation of L929 cells without affecting their viability was confirmed by MTT assay. The results of the present research suggests the possibility to use herbal combination as source for plausible antibacterial agent which could be isolated and used as a lead candidate for the development of antibacterial drug that help to limit or stop infectious illnesses caused by different pathogenic microbes.

Effectiveness and safety of tofacitinib for ulcerative colitis: two-year results of the ICC Registry.

BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. AIM: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. METHODS: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 µg/g), safety, and discontinuation rate. RESULTS: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. CONCLUSION: Tofacitinib was effective in 31.8% of patients after 24 months of treatment.

Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study.

BACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. METHODS: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 µg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P < .01; OR, 3.02; 95% CI, 1.89-4.84; P < .01; and OR, 1.86; 95% CI, 1.15-2.99; P = .01; and OR, 3.27; 95% CI, 1.96-5.45; P < .01; OR, 1.87; 95% CI, 1.14-3.07; P = .01; and OR, 1.81; 95% CI, 1.06-3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events. CONCLUSIONS: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes.

Recent advances to overcome the burden of Japanese encephalitis: A zoonotic infection with problematic early detection.

Japanese encephalitis (JE) is a vector-borne neurotropic disease caused by Japanese encephalitis virus (JEV) associated with high mortality rate distributed from Eastern and Southern Asia to Northern Queensland (Australia). The challenges in early detection and lack of point-of-care biomarkers make it the most important Flavivirus causing encephalitis. There is no specific treatment for the disease, although vaccines are licenced. In this review, we focussed on point-of-care biomarkers as early detection tools and developing the effective therapeutic agents that could halt JE. We have also provided molecular details of JEV, disease progression, and its pathogenesis with recent findings which might bring insights to overcome the disease burden.

Silica nanoparticles as novel sustainable approach for plant growth and crop protection.

Agriculture crops encounter several biotic and abiotic stresses, including pests, diseases, nutritional deficits, and climate change, which necessitate the development of new agricultural technologies. By developing nano-based fertilizers, insecticides and herbicides, and early disease diagnostics, nanotechnology may help to increase agricultural crop quality and production. The application of silica nanoparticles (SiNPs) may be the solution for increasing the yield to combat the agriculture crisis in the near future. SiNPs have unique physiological properties, such as large surface area, aggregation, reactivity, penetrating ability, size, and structure, which enable them to penetrate plants and regulate their metabolic processes. Pesticide delivery, enhanced nutrition supply, disease management, and higher photosynthetic efficiency and germination rate are all attributed to SiNPs deposition on plant tissue surfaces. SiNPs have been demonstrated to be non-toxic in nature, making them suitable for usage in agriculture. In this regard, the current work provides the most important and contemporary applications of SiNPs in agriculture as well as biogenic and non-biogenic synthetic techniques. As a result, this review summarizes the literature on SiNPs and explores the use of SiNPs in a variety of agricultural disciplines.

Th1-Th2 and M1-M2 interplay sculpt Aeromonas hydrophila pathogenesis in zebrafish (Danio rerio).

Aeromonas hydrophila is an important aquatic zoonotic pathogen that causes septicemia, necrotizing fasciitis and gastroenteritis in various aquatic and non-aquatic animals. However, the pathogenesis of A. hydrophila is not fully understood. Here, we examined the pathogenicity and histopathology of A. hydrophila in the zebrafish (Danio rerio) model system. We found that the intensity of symptoms and mortality is dose-dependent. Bacterial colonization studies demonstrated that A. hydrophila never cleared out from the fish body but stayed in a state of inactivity till it enters a fresh host. Reinfection studies showed that exposure to A. hydrophila provides immunity against future infection and hence improves fish survival. Gene expression studies revealed the crosstalk between T-helper cell and macrophage responses in fish immune system in response to A. hydrophila and infection memory. Histopathological studies showed that symptoms of tissue damage and inflammation lasted for less duration with less intensity in immunized fish when compared to non-immunized fish. Together, our results suggest that the zebrafish model is a useful system in studying the interplay between A. hydrophila pathogenesis, persistence and immunity.

Surface plasmon resonance: A promising approach for label-free early cancer diagnosis.

Cancer is the second leading cause of death worldwide after cardiovascular disease. The major cause of high mortality is delayed detection. Therefore, detection at an early stage followed by early treatment can mitigate morbidity as well as mortality. The utilization of biomarker-based detection tools helps in early-stage recognition. Fortunately, biomarkers indicating disease status are released in to the circulation. These include traditional marker proteins as well as exosomes, micro-RNA (miRNA) and circulating tumor DNA (ct-DNA). Biosensors are biological and chemical reaction devices that generate signals based on analyte concentration. Due to analyte binding, these devices demonstrate high sensitivity and specificity. This review examines the use of surface plasmon resonance (SPR)-based sensors in the diagnosis of various cancer including those of the breast, prostate, lung, ovary, cervix and pancreas. SPR is a label-free, real-time and non-invasive optical biosensing technology representing a novel diagnostic tool in cancer detection.

Natural Biosurfactant as Antimicrobial Agent: Strategy to Action Against Fungal and Bacterial Activities.

Natural surfactants have gained importance as the usage of synthetic surfactants shows economical aspects, health, and environmental effect. This study examined the anti-microbial activity of safflower seed waste (Ssw) isolated surfactant against dandruff-causing Malassezia furfur and skin diseases causing bacterial strains. Saponin was the major component and non-ionic surfactants derived from plants, which have a special molecular structure with hydrophilic glycoside backbone and lipophilic triterpene derivative. The antimicrobial activity of isolated surfactants was confirmed by the MIC and kill-time assays. Our results showed that the isolated saponin may interact with the cell wall and membrane first and destroy the cell wall and membranes, which finally results in bacterial death. Besides, isolated saponin penetrates the cytoplasmic membrane or enters inside the cell after the destruction of cell structure, and then inhibits the normal synthesis of DNA and proteins that are required for bacterial growth. These results suggested that the effects of the Ssw isolated saponin on the growth inhibition of selected bacterial strains may be at the molecular level rather than only physical damage. Extraction of Biosurfactant (saponin) from Safflower seed waste and its antimicrobial activity.

Micelles in Cancer Therapy: An Update on Preclinical and Clinical Status.

BACKGROUND: In the recent years, Micelles represent a promising carrier for the treatment and diagnosis of cancer. Architecturally, micelles are self-assembled nanosized colloidal aggregates prepared from amphiphilic surfactant with a hydrophobic core and hydrophilic shell. Such a composition makes them a potential carrier for delivery of hydrophobic anticancer drugs with in their core. METHODS: Micelles have received increasing interest as an enhanced permeability and retention (EPR) targeted drug delivery systems for cancer treatment. Micelles can be modified to contribute various attractive properties, for instance, active targeting, stimuli-responsiveness. They have also proven their ability in drug targeting to tumor tissue, enhanced drug accumulation, drug stabilization, tissue penetration, prolong circulation, in vivo biocompatibility, biodegradability and reduced side effects. Micelles have displayed a vital role in multidrug delivery for cancer therapy. RESULTS AND DISCUSSION: The aim of the present review is to provide an overview on the status of micellar nanoformulations for anticancer agents, including their pre-clinical and clinical researches. Emphasis is placed on presenting the newer strategies to enhance the therapeutic efficacy of anticancer drug at the target site. The type of co-polymers used and methods for the preparation of micelles are also highlighted in the paper.

Effects of Prednisolone Derivative and Panaxydol: Biosurfactants on Cell Wall Integrity of Acne-Causing Resistant Bacteria.

Acne is one of the most common dermatological skin problem caused due to inflammation of the skin, leading to unfavorable growth of Propionibacterium acnes. It is a slow growing anaerobic, gram-positive bacterium that releases chemotactic factors and leads to the complex pathogenicity of acne. There are several acne treatments/therapies available, but topical therapy is usually the first choice for mild to moderate acne, and as the severity of the acne increases, the treatment modalities fail. There are many acne treatment options available, but topical therapy is best suited for mild - to - moderate skin problems, and then as the seriousness of the acne grows, the therapeutic approaches fall short. Biosurfactants are surfactants produced from plants or animals; Saponins are plant derived non-ionic biosurfactants which have steroidal and triterpenic glycosides distributed largely in plant kingdom. Numerous studies conducted by scientists have established the antimicrobial activity of and are considered more advantageous over synthetic precursors as they are eco-friendly, cheap and non-toxic. The present study was undertaken to investigate the antibacterial activity of saponins (bio-surfactants) characterized using mass spectroscopy against acne-causing bacteria. The discharge of cellular components including protein and UV-sensitive materials in the cell-free supernatant was provoked by saponin, confirming the cellular and membrane disturbances.. Furthermore, various morphological changes on the bacterial cell surface structure by Transmission electron microscopy and scanning electron microscopy revealed the disruption of the cell integrity leading to death. Results confirmed presence of non-ionic surfactants primarily affecting the disruption and destruction to the bacteria which indicates that saponins are efficient components with great potential applications in various pharmaceutical preparations. Effects of Prednisolone derivative and Panaxydol: Biosurfactants on cell wall integrity of Acne-Causing Resistant Bacteria.

Pentalinonsterol, a Phytosterol from Pentalinon andrieuxii, is Immunomodulatory through Phospholipase A2 in Macrophages toward its Antileishmanial Action.

Our earlier in vitro and in vivo studies have revealed that the phytosterol, pentalinonsterol (cholest-4,20,24-trien-3-one) (PEN), isolated from the roots of Pentalinon andrieuxii, possesss immunomodulatory properties in macrophages and dendritic cells. Leishmaniasis, caused by the infection of Leishmania spp. (a protozoan parasite), is emerging as the second-leading cause of mortality among the tropical diseases and there is an unmet need for a pharmacological intervention of leishmaniasis. Given the beneficial immunomodulatory actions and lipophilic properties of PEN, the objective of this study was to elucidate the mechanism(s) of action of the immunomodulatory action(s) of PEN in macrophages through the modulation of phospholipase A2 (PLA2) activity that might be crucial in the antileishmanial action of PEN. Therefore, in this study, we investigated whether PEN would modulate the activity of PLA2 in RAW 264.7 macrophages and mouse bone marrow-derived primary macrophages (BMDMs) in vitro and further determined how the upstream PLA2 activation would regulate the downstream cytokine release in the macrophages. Our current results demonstrated that (i) PEN induced PLA2 activation (arachidonic acid release) in a dose- and time-dependent manner that was regulated upstream by the mitogen-activated protein kinases (MAPKs); (ii) the PEN-induced activation of PLA2 was attenuated by the cPLA2-specific pharmacological inhibitors; and (iii) the cPLA2-specific pharmacological inhibitors attenuated the release of inflammatory cytokines from the macrophages. For the first time, our current study demonstrated that PEN exhibited its immunomodulatory actions through the activation of cPLA2 in the macrophages, which potentially could be used in the development of a pharmacological intervention against leishmaniasis.

Cliv-92-Loaded Glycyrrhetinic Acid-Modified Chitosan Nanoparticles for Enhanced Hepatoprotection-Preparation, Characterization, and In Vivo Evaluation.

Cliv-92 is a mixture of three structurally similar coumarinolignoids and a proven hepatoprotective agent. Low aqueous solubility and poor bioavailability are notable hindrances for its further use. Therefore, glycyrrhetinic acid-linked chitosan nanoparticles loaded with Cliv-92 were prepared for active targeting to the liver. The nanoparticles were prepared by the ionic gelation method to avoid the use of toxic solvents/rigorous agitation. The method of preparation was optimized using a central composite design with independent variables, namely polymer: drug ratio (3:1, w/w), crosslinker concentration (0.5%), and stirring speed (750 rpm). The optimized nanoparticles had a mean particle size of 185.17 nm, a polydispersity index of 0.41, a zeta potential of 30.93 mV, and a drug loading of 16.30%. The prepared formulation showed sustained release of approximately 63% of loaded Cliv-92 over 72 h. The nanoparticles were freeze-dried for long-term storage and further characterized. The formulation was found to be biocompatible for parenteral delivery. In vivo imaging study showed that optimized nanoparticles were preferentially accumulated in the liver and successfully targeting the liver. The present study successfully demonstrated the improved pharmacokinetic properties (≈12% relative bioavailability) and efficacy profile (evidenced by in vivo and histopathological studies) of fabricated Cliv-92 nanoparticles.