Exploring the immunomodulatory potential of Brahmi (Bacopa monnieri) in the treatment of invasive ductal carcinoma.

Bacopa monnieri (L) Wettst, commonly known as Brahmi, stands as a medicinal plant integral to India's traditional medical system, Ayurveda, where it is recognized as a "medhya rasayana"-a botanical entity believed to enhance intellect and mental clarity. Its significant role in numerous Ayurvedic formulations designed to address conditions such as anxiety, memory loss, impaired cognition, and diminished concentration underscores its prominence. Beyond its application in cognitive health, Brahmi has historically been employed in Ayurvedic practices for the treatment of inflammatory diseases, including arthritis. In contemporary biomedical research, Bacopa monnieri can attenuate the release of pro-inflammatory cytokines TNF-α and IL-6 in animal models. However, there remains a paucity of information regarding Bacopa's potential as an anticancer agent, warranting further investigation in this domain. Based on previous findings with Brahmi (Bacopa monnieri), the current study aims to find out the role of Brahmi plant preparation (BPP) in immunomodulatory actions on IDC. Employing a specific BPP concentration, we conducted a comprehensive study using MTT assay, ELISA, DNA methylation analysis, Western blotting, ChIP, and mRNA profiling to assess BPP's immunomodulatory properties. Our research finding showed the role of BPP in augmenting the action of T helper 1 (TH1) cells which secreted interferon-γ (IFN-γ) which in turn activated cytotoxic T-lymphocytes (CTL) to kill the cells of IDC (*p < 0.05). Moreover, we found out that treatment with BPP not only increased the activities of tumor-suppressor genes (p53 and BRCA1) but also decreased the activities of oncogenes (Notch1 and DNAPKcs) in IDC (*p < 0.05). BPP had an immense significance in controlling the epigenetic dysregulation in IDC through the downregulation of Histone demethylation & Histone deacetylation and upregulation of Histone methylation and Histone acetylation (*p < 0.05). Our Chromatin immunoprecipitation (ChIP)-qPCR data showed BPP treatment increased percentage enrichment of STAT1 & BRCA1 (*p < 0.05) and decreased percentage enrichment of STAT3, STAT5 & NF ΚB (*p < 0.05) on both TBX21 and BRCA1 gene loci in IDC. In addition, BPP treatment reduced the hypermethylation of the BRCA1-associated-DNA, which is believed to be a major factor in IDC (*p < 0.05). BPP not only escalates the secretion of type 1 specific cytokines but also escalates tumor suppression and harmonizes various epigenetic regulators and transcription factors associated with Signal Transducer and Activator of Transcription (STAT) to evoke tumor protective immunity in IDC.

Mannose-Anchored Nano-Selenium Loaded Nanostructured Lipid Carriers of Etravirine for Delivery to HIV Reservoirs.

The present investigation aims to develop and explore mannosylated lipid-based carriers to deliver an anti-HIV drug, Etravirine (TMC) and Selenium nanoparticles (SeNPs), to the HIV reservoirs via the mannose receptor. The successful mannosylation was evaluated by the change in zeta potential and lectin binding assay using fluorescence microscopy. Electron microscopy and scattering studies were employed to study the structure and surface of the nanocarrier system. The presence of selenium at the core-shell of the nanocarrier system was confirmed by X-ray photoelectron spectroscopy and energy dispersive X-ray analysis. Further, the in vitro anti-HIV1 efficacy was assessed using HIV1 infected TZM-bl cells followed by in vivo biodistribution studies to evaluate distribution to various reservoirs of HIV. The results exhibited higher effectiveness and a significant increase in the therapeutic index as against the plain drug. The confocal microscopy and flow cytometry studies exhibited the efficient uptake of the coumarin-6 tagged respective formulations. The protective effect of nano selenium toward oxidative stress was evaluated in rats, demonstrating the potential of the lipidic nanoparticle-containing selenium in mitigating oxidative stress in all the major organs. The in vivo biodistribution assessment in rats showed a 12.44, 8.05 and 9.83-fold improvement in the brain, ovary, and lymph node biodistribution, respectively as compared with plain TMC. Delivery of such a combination via mannosylated nanostructured lipid carriers could be an efficient approach for delivering drugs to reservoirs of HIV while simultaneously reducing the oxidative stress induced by such long-term therapies by co-loading Nano-Selenium.

Etravirine-loaded dissolving microneedle arrays for long-acting delivery.

A key challenge of HIV treatment with multiple antiretroviral drugs is patient adherence. Thus, there is an urgent need for long-acting depot systems for delivering drugs over an extended duration. Although the parenteral route is preferred for depot systems, it is associated with obvious drawbacks, such as painful injections, potentially-contaminated sharps waste, and the necessity of trained healthcare personnel for administration. Amongst a small number of alternatives in development microneedles are versatile delivery systems enabling systemic drug delivery and potentially improving patient adherence due to their capacity for self-administration. We have developed dissolving microneedle (DMNs) embedded with etravirine nanosuspension (ETR NS) as a long-acting HIV therapy to improve patient adherence. The ETR NS prepared by sonoprecipitation yielded particle sizes of 764 ± 96.2 nm, polydispersity indices of of 0.23 ± 0.02, and zeta potentials of -19.75 ± 0.55 mV. The DMNs loaded with ETR NS demonstrated 12.84 ± 1.33% ETR deposition in ex-vivo neonatal porcine skin after 6 h application. In in vivo rat pharmacokinetic studies, the Cmax exhibited by DMNs loaded with ETR powder and ETR NS were 158 ± 10 ng/mL and 177 ± 30 ng/mL, respectively. DMN groups revealed a higher t1/2, Tmax, and mean residence time compared to intravenous ETR solutions, suggesting the long-acting potential of etravirine delivered intradermally using DMNs.

The acute effects of decaffeinated versus caffeinated coffee on reaction time, mood and skeletal muscle strength.

Background Caffeinated coffee, a psycho-stimulant, is widely consumed throughout the globe. However, its chronic consumption has deleterious effects on human health. Meanwhile, decaffeinated coffee has low content of caffeine and thus can be an alternative to caffeinated coffee. Therefore, the study was undertaken to explore and compare the acute effects of decaffeinated and caffeinated coffee on reaction time, mood and skeletal muscle strength in healthy volunteers. Methods This was a prospective, interventional, comparative type of study. The study included 70 healthy adults divided into two groups (Caffeinated coffee group and Decaffeinated coffee group). The following parameters were assessed: reaction time was assessed by digital display multiple-choice apparatus, mood by Visual Analogue Scale (VAS) and Profile of Mood States revised version (POMS) and skeletal muscle strength by hand dynamometer. All parameters in both groups were assessed pre-intervention (baseline) and 30 min post-intervention. Results In both groups (decaffeinated and caffeinated coffee) post-intervention, there was a statistically significant (p < 0.05) improvement in the reaction time (VRT) and mood (VAS, POMS) from the baseline. However, both groups did not show any significant effects on the skeletal muscle strength. Upon comparing the two groups, we found that caffeinated coffee showed higher and significant improvement of mood than decaffeinated coffee. Conclusions Decaffeinated coffee exerts an acute significant stimulatory effect on the reaction time and mood. However, these effects in comparison to caffeinated coffee are low. Further randomized control clinical trials are thus needed to validate these interesting findings.

Identification of Differentially Regulated Edwardsiella ictaluri Proteins During Catfish Serum Treatment.

Edwardsiella ictaluri is a facultative, intracellular, gram-negative bacterium that causes enteric septicemia of catfish (ESC). Edwardsiella ictaluri is known to be resistant to defense mechanisms present in catfish serum, which might aid in its use of a host's bloodstream to become septicemic. However, the precise mechanisms of the survival of E. ictaluri in host serum are not known. Analysis of the response of E. ictaluri to the host serum treatment at a proteomic level might aid in the elucidation of its adaptation mechanisms against defense mechanisms present in catfish serum. Thus, the objective of this study was to identify differentially regulated proteins of E. ictaluri upon exposure to naïve catfish serum. Two-dimensional difference gel electrophoresis (2D-DIGE) followed by in-gel trypsin digestion and MALDI-TOF/TOF analysis were used for identification of differentially expressed E. ictaluri proteins. A total of 19 differentially regulated proteins (7 up- and 12 downregulated) were identified. Among those were four putative immunogenic proteins, two chaperones and eight proteins involved in the translational process, two nucleic acid degradation and integration proteins, two intermediary metabolism proteins, and one iron-ion-binding protein. Further research focusing on the functions of these differentially expressed proteins may reveal their roles in host adaptation by E. ictaluri.

Canola engineered with a microalgal polyketide synthase-like system produces oil enriched in docosahexaenoic acid.

Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, neither has been produced in commercially relevant amounts in a widely grown crop. We report expression of a microalgal polyketide synthase-like PUFA synthase system, comprising three multidomain polypeptides and an accessory enzyme, in canola (Brassica napus) seeds. This transgenic enzyme system is expressed in the cytoplasm, and synthesizes DHA and EPA de novo from malonyl-CoA without substantially altering plastidial fatty acid production. Furthermore, there is no significant impact of DHA and EPA production on seed yield in either the greenhouse or the field. Canola oil processed from field-grown grain contains 3.7% DHA and 0.7% EPA, and can provide more than 600 mg of omega-3 LC-PUFAs in a 14 g serving.

Novel L-lactide-depsipeptide polymeric carrier for enhanced brain uptake of rivastigmine in treatment of Alzheimer's disease.

The present study discusses possibility of targeting an anti-Alzheimer's drug rivastigmine tartarate (RT) to the brain using novel synthesized L-lactide-depsipeptide polymeric nanoparticles (NPs). Single emulsion-solvent evaporation technique was used for preparation of NPs. The mean particle size, zeta potential and entrapment efficiency of drug loaded NPs were found to be 142.2 +/- 21.3 nm, +4.85 mV and 60.72 +/- 3.72% respectively. Pharmacodynamic study showed faster regain of memory loss in amnesic rat with RT loaded NPs as compared to RT solution. In pharmacokinetic study, total concentration and mean residence time was increased up to 3.79 fold and 2 fold respectively while clearance was decreased to 1.91 fold on intravenous administration of RT loaded NPs as compared to RT solution. The biodistribution study demonstrated 5.45 fold and 2 fold increase in brain concentration of drug after administration of RT loaded NPs (i.v; 10.52 +/- 1.31 ng/ml) as compared to plain RT solution by oral (1.93 +/- 1.23 ng/ml) and intravenous (5.34 +/- 1.22 ng/ml) route, respectively. Therefore, RT loaded L-lactide-depsipeptide polymeric NPs might be a potential drug delivery system in treatment of Alzheimer's disease.

Social determinants of stunting in rural area of Wardha, Central India.

BACKGROUND: Stunting is a consequence of long term, cumulative inadequacies of health and nutrition. Health system uses underweight for growth monitoring for its simplicity. Lately there is renewed interest in stunting and especially severe acute malnutrition. Stunting is a relatively neglected indicator. It is therefore imperative to understand the causes of stunting early in infancy and childhood, so that preventive measures can be taken. Hence, the present study was undertaken to study the social determinants of stunting in rural Wardha. METHODS: The present cross-sectional study was undertaken in three Primary Health Centres (PHCs) of Wardha district with total population of 88,187. The sample was drawn from three PHC areas by 30-cluster sampling technique. Stunting was defined using WHO Child Growth Standards for 'height-for-age'. 'Height-for-age' values below 2 standard deviations were considered as stunted while below 3 standard deviations were considered 'severe stunting'. RESULT: Prevalence of stunting was observed to be 52.3% and severe stunting was 25.1%. The significant determinants of stunting were found to be age, father's education, fathers' occupation, low income, not receiving Vitamin-A supplement during last 6 months and having anaemia. Sex, caste, mother's education and mothers' occupation did not contribute significantly to the stunting. CONCLUSION: Low income and related factors such as father's education and his occupation are important determinant of the stunting. Father being the decision maker, his education is of importance. Vitamin-A supplementation and anaemia as surrogate indicators for access to health care also found out to be significant determinants of stunting.

Rice germ oil as multifunctional excipient in preparation of self-microemulsifying drug delivery system (SMEDDS) of tacrolimus.

Surmounting the constraints of limited solubilization efficiency and prime requisite of antioxidant for conventional lipid formulations, the research work explores an edge over formulation utilizing potential applicability of rice germ oil (RGO) as a multifunctional excipient. Self-microemulsifying drug delivery system (SMEDDS) of tacrolimus (TAC) was formulated with RGO, an indigenous source of gamma-oryzanol. Being the same biological source, RGO and rice bran oil (RBO) were compared and it was found that RGO have more solubilization potential for TAC (2.2-fold) as well as higher antioxidant activity (8.06-fold) than the RBO. TAC-SMEDDS was prepared using RGO/Capmul PG8 (2:3) as an oil phase, Cremophore EL as a surfactant, and Transcutol P as a cosurfactant. The approximate particle size of TAC-SMEDDS was found to be 38 nm by dynamic light scattering and 12 nm by small angle neutron scattering. The in vitro dissolution studies showed complete and rapid drug release in 30 min compared to a plain drug (<5%) and marketed capsule (<50%). AUC and C(max) were found to be 45.05 ± 15.64 ng h/ml and 3.91 ± 1.2 ng/ml for TAC-SMEDDS, 12.59 ± 5.54 ng h/ml and 0.48 ± 0.12 ng/ml for plain TAC, and 30.23 ± 10.34 ng h/ml and 2.31 ± 0.68 ng/ml for marketed formulation, respectively. The improved pharmacokinetic profile of TAC-SMEDDS is correlating to the dissolution results. Thus, gamma-oryzanol-enriched RGO acts as a potential multifunctional excipient for lipid formulations.

Felodipine ß-cyclodextrin complex as an active core for time delayed chronotherapeutic treatment of hypertension.

The present research work deals with the development of a time delayed chronotherapeutic formulation of felodipine (FD) aimed at rapid drug release after a desired lag time in the management of hypertension. The developed system comprises a drug core embedded within a swellable layer and coated with an insoluble, water permeable polymeric system. FD cyclodextrin complex was used as an active core while ethyl cellulose was used as an effective coating layer. Dissolution studies of the complex revealed that there was a 3-fold increase in dissolution of the complex compared to plain FD. This dissolution enhancement and rapid drug release resulted from FD amorphisation, as confirmed by XRD, DSC and SEM studies. FTIR and ¹H NMR studies confirmed the complex formation between FD and cyclodextrin based on the observed hydrogen bond interactions. FD release was adequately adjusted by using a pH independent polymer, i.e., ethyl cellulose, along with dibutyl phthalate as plasticizer. Influence of formulation variables like polymer viscosity, plasticizer concentration, super disintegrant concentration in the swellable layer and percent coating weight gain was investigated to characterize the lag time. Upon permeation of water, the core tablet swelled, resulting in the rupture of the coating layer, followed by rapid drug release. The developed formulation of FD showed a lag time of 5-7 h, which is desirable for chronotherapeutic application.

High-k dielectric Al2O3 nanowire and nanoplate field effect sensors for improved pH sensing.

Over the last decade, field-effect transistors (FETs) with nanoscale dimensions have emerged as possible label-free biological and chemical sensors capable of highly sensitive detection of various entities and processes. While significant progress has been made towards improving their sensitivity, much is yet to be explored in the study of various critical parameters, such as the choice of a sensing dielectric, the choice of applied front and back gate biases, the design of the device dimensions, and many others. In this work, we present a process to fabricate nanowire and nanoplate FETs with Al(2)O(3) gate dielectrics and we compare these devices with FETs with SiO(2) gate dielectrics. The use of a high-k dielectric such as Al(2)O(3) allows for the physical thickness of the gate dielectric to be thicker without losing sensitivity to charge, which then reduces leakage currents and results in devices that are highly robust in fluid. This optimized process results in devices stable for up to 8 h in fluidic environments. Using pH sensing as a benchmark, we show the importance of optimizing the device bias, particularly the back gate bias which modulates the effective channel thickness. We also demonstrate that devices with Al(2)O(3) gate dielectrics exhibit superior sensitivity to pH when compared to devices with SiO(2) gate dielectrics. Finally, we show that when the effective electrical silicon channel thickness is on the order of the Debye length, device response to pH is virtually independent of device width. These silicon FET sensors could become integral components of future silicon based Lab on Chip systems.

Community-led initiative for control of anemia among children 6 to 35 months of age and unmarried adolescent girls in rural Wardha, India.

BACKGROUND: Studies in India have reported a high prevalence of nutritional anemia among children and adolescent girls. Nutritional anemia is associated with impaired mental, physical, and cognitive performance in children and is a significant risk factor for maternal mortality. OBJECTIVE: To evaluate the effect of a community-led initiative for control of nutritional anemia among children 6 to 35 months of age and unmarried rural adolescent girls 12 to 19 years of age. METHODS: This Participatory Action Research was done in 23 villages of the Primary Health Centre, Anji, in Wardha District of Maharashtra. In February and March 2008, needs assessment was undertaken by interviewing the mothers of 261 children and 260 adolescent girls. Hemoglobin levels of adolescent girls and children were measured with the use of the hemoglobin color scale. The girls were given weekly iron-folic acid tablets, and the children were given daily liquid iron prophylaxis for 100 days in a year through community participation. The adolescent girls and the mothers of the children and adolescent girls were also given nutritional education on the benefits and side effects of iron supplementation. In June and July 2008, follow-up assessment was performed by survey and force field analysis. RESULTS: There was a significant reduction in the prevalence of nutritional anemia from 73.8% to 54.6% among the adolescent girls and from 78.2% to 64.2% among the children. There was improvement in awareness of iron-rich food items among the adolescent girls and the mothers of the children. The benefits to girls, such as increase in appetite and reduction in scanty menses, tiredness, and weakness, acted as positive factors leading to better compliance with weekly iron supplementation. The benefits to children perceived by the mothers, such as increase in appetite, weight gain, reduction in irritability, and reduction in mud-eating behavior, acted as a dominant positive force and generated demand for iron syrup. CONCLUSIONS: The community-led initiative for once-weekly iron supplementation for adolescent girls and iron prophylaxis for children, in addition to nutritional education, improved the hemoglobin status of children 6 to 35 months of age and unmarried rural adolescent girls 12 to 19 years of age.

A community based approach to improve health care seeking for newborn danger signs in rural Wardha, India.

OBJECTIVE: To find out the effect of community mobilization and health education effort on health care seeking behavior of families with sick newborns, and to explore the rationale behind the changed health care seeking behaviors of mothers in a rural Indian community. METHODS: In the present community based participatory intervention, a triangulated research design of quantitative (survey) and qualitative (Focus group discussions, FGDs) method was undertaken for needs assessment in year 2004. In community mobilization, women's self help groups; Kishori Panchayat (KP, forum of adolescent girls), Kisan Vikas Manch (Farmers' club) and Village Coordination Committees (VCC) were formed in the study area. The trained social worker facilitated VCCs to develop village health plans to act upon their priority maternal and child health issues. The pregnant women and group members were given health education. The Lot Quality Assurance Sampling (LQAS) technique was used to monitor awareness regarding newborn danger signs among pregnant women. In year 2007, a triangulation of quantitative survey and a qualitative study (free list and pile sort exercise) was undertaken to find out changes in health care seeking behaviors of mothers. RESULTS: There was significant improvement in mothers' knowledge regarding newborn danger signs. About half of the mothers got information from CLICS doot (female community health worker). The monitoring over three years period showed encouraging trend in level of awareness among pregnant women. After three years, the proportion of mothers giving no treatment/home remedy for newborn danger signs declined significantly. However, there was significant improvement in mothers' health care seeking from private health care providers for sick newborns. CONCLUSION: The present approach improved mothers' knowledge regarding newborn danger signs and improved their health care seeking behavior for newborn danger signs at community level. Due to lack of faith in government health services, women preferred to seek care from private providers.

Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate.

The present work was aimed at formulating a SMEDDS (self-microemulsifying drug delivery system) of fenofibrate and evaluating its in vitro and in vivo potential. The solubility of fenofibrate was determined in various vehicles. Pseudoternary phase diagrams were used to evaluate the microemulsification existence area, and the release rate of fenofibrate was investigated using an in vitro dissolution test. SMEDDS formulations were tested for microemulsifying properties, and the resultant microemulsions were evaluated for clarity, precipitation, and particle size distribution. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The optimized formulation for in vitro dissolution and pharmacodynamic studies was composed of Labrafac CM10 (31.5%), Tween 80 (47.3%), and polyethylene glycol 400 (12.7%). The SMEDDS formulation showed complete release in 15 minutes as compared with the plain drug, which showed a limited dissolution rate. Comparative pharmacodynamic evaluation was investigated in terms of lipid-lowering efficacy, using a Triton-induced hypercholesterolemia model in rats. The SMEDDS formulation significantly reduced serum lipid levels in phases I and II of the Triton test, as compared with plain fenofibrate. The optimized formulation was then subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable over 12 months. Thus, the study confirmed that the SMEDDS formulation can be used as a possible alternative to traditional oral formulations of fenofibrate to improve its bioavailability.

Acrylate-based transdermal therapeutic system of nitrendipine.

The objective of the present research investigation was to fabricate an acrylate-based transdermal therapeutic system (TTS) of nitrendipine, which could deliver drug at maximum input rate so as to deliver drug in minimum patch size. Transdermal patches were fabricated using synthesized acrylate pressure-sensitive adhesives (PSAs): PSA1, PSA2, and commercially available PSA3 and PSA4 using d-limonene as permeation enhancer. Effect of concentration of d-limonene on permeation kinetics of nitrendipine in PSAs was studied. Fabricated TTS in mentioned PSAs were evaluated for in-vitro release and permeation kinetics through guinea-pig skin. Cumulative release of drug in PSA1, PSA2, PSA3, and PSA4 was observed to be 45%, 40%, 25%, and 25%, respectively, upto 24 hr. Flux of drug through guinea-pig skin calculated at 48 hr in PSA1, PSA2, PSA3, and PSA4, with and without d-limonene, was observed to be 0.346+/-0.10, 0.435+/-0.17, 0.410+/-0.17, and 0.162+/-0.06, and 0.625+/-0.19, 1.161+/-0.46, 0.506+/-0.17, and 0.520+/-0.18 (microg/cm2/hr), respectively. The TTS in PSA2 showed comparatively high flux and could deliver drug at high input rate through transdermal route. PSA2 was found to have good rate-controlling property and could be successfully employed in transdermal delivery of nitrendipine.