Enhanced efficacy of ß-carotene loaded solid lipid nanoparticles optimized and developed via central composite design on breast cancer cell lines.

ß-carotene is obtained from both plants and animals and has been the subject of intense research because of its provitamin-A, antioxidant, and anticancer effects. Its limited absorption and oxidative degradation significantly reduce its antitumor efficacy when taken orally. In our study, we utilize a central composite design to develop "bio-safe and highly bio-compatible" solid lipid nanoparticles (SLNs) by using only the combination of palmitic acid and poloxamer-407, a block co-polymer as a surfactant. The current research aim to develop and characterize SLNs loaded with ß-carotene to improve their bioavailability and therapeutic efficacy. In addition, the improved cytotoxicity of solid lipid nanoparticles loaded with ß-carotene was screened in-vitro in human breast cancer cell lines (MCF-7). The nanoparticles exhibits good stability, as indicated by their mean zeta potential of -26.3 ± 1.3 mV. The particles demonstrated high drug loading and entrapment capabilities. The fabricated nanoparticle's prolonged release potential was shown by the in-vitro release kinetics, which showed a first-order release pattern that adhered to the Higuchi model and showed a slow, linear, and steady release over 48 h. Moreover, a diffusion-type release mechanism was used to liberate ß-carotene from the nanoparticles. For six months, the nanoparticles also showed a notable degree of physical stability. Lastly, using the MTT assay, the anti-cancer properties of ß-carotene-loaded solid lipid nanoparticles were compared with intact ß-carotene on MCF-7 cell lines. The cytotoxicity tests have shown that the encapsulation of ß-carotene in the lipid bilayers of the optimized formulation does not interfere with the anti-cancer activity of the drug. When compared to standard ß-carotene, ß-carotene loaded SLNs showed enhanced anticancer efficacy and it is a plausible therapeutic candidate for enhancing the solubility of water-insoluble and degradation-sensitive biotherapeutics like ß-carotene.

Essential oils extracted from Citrus macroptera and Homalomena aromatica (Spreng.) Schott. exhibit repellent activities against Aedes aegypti (Diptera: Culicidae).

BACKGROUND OBJECTIVES: Mosquitoes alone transmit diseases to around 700 million individuals annually, killing approximately 0.7 million people every year worldwide. Considering the potential health risks linked with synthetic repellents, it has become vital to identify eco-friendly, natural repellents for mosquito control as well as to understand the underlying mechanism for mosquito repellent activity. To address this, objectives were set to extract essential oils from Citrus macroptera peel and Homalomena aromatica (Spreng.) Schott. rhizomes, evaluate their mosquito repellent activity against Aedes aegypti, and further explore their mosquito odorant receptor inhibition potential. METHODS: The oils were extracted using Clevenger's apparatus, and properties like specific gravity, refractive index, and boiling point were evaluated and characterised using Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectroscopy (GC-MS). Aedes aegypti mosquito eggs collected from the Indian Council of Medical Research (ICMR), Dibrugarh, were reared in the Department of Pharmaceutical Sciences, Research Laboratory, to obtain adult Aedes aegypti mosquitoes for the mosquito repellent activity evaluation of the essential oils using the Human Bait technique'. Molecular docking studies were performed for the oil components against mosquito odorant binding proteins. Further, toxicity studies of these two oils were evaluated against human dermal fibroblast adult (HDFa) cells. RESULTS: The results revealed the presence of limonene (86.76%) and linalool (52.35%), respectively, in Citrus macroptera and Homalomena aromatica oils. It was found that the combination of the oils in a ratio of 1:1 showed mosquito repellent activity for up to 6.33 ± 0.23 h. Molecular docking studies showed the presence of major oil components having mosquito odorant receptor blocking potential comparable to N, N-diethyl-meta-toluamide (DEET), indicating a rationale for extended mosquito repellent action. Further, both of these oils were found to be non-cytotoxic against HDFa cells after 24 h. INTERPRETATION CONCLUSION: The encouraging mosquito repellent activity of these two oils as compared to synthetic mosquito repellent DEET might pave the way for the development of novel herbal mosquito repellent formulations containing these essential oils.

A Novel Report of mycetoma with Spinal Spread due to Madurella fahalli from India.

Eumycetoma caused by Madurella fahalii, a drug-resistant fungus, has never been reported in India. Here, we describe a fatal case of eumycetoma with spinal involvement due to M. fahalii for the first time in India.

Correction: Identification of Lasiodiplodia species inciting stem rot of dragon fruit in India through polyphasic approach.

[This corrects the article DOI: 10.1007/s13205-023-03754-1.].

Identification of Lasiodiplodia species inciting stem rot of dragon fruit in India through polyphasic approach.

Lasiodiplodia species commonly thrive as endophytes, saprobes, and plant pathogens in tropical and subtropical regions. Association of Lasiodiplodia species causing stem rot in dragon fruit in the coastal belt of Odisha, eastern India, has been illustrated here. The stem rot disease was characterized by yellowing of the stem, followed by softening of the stem tissues with fungal fructifications of the pathogen in the affected tissues. On the basis of macro- and micromorphological characteristics, the four fungal isolates recovered from diseased stems were identified initially as Lasiodiplodia species. By comparing DNA sequences within the NCBI GenBank database as well as performing a multigene phylogenetic analysis involving the internal transcribed spacer region (ITS-rDNA), ß-tubulin (ß-tub), and elongation factor-alpha (EF1-α) genes, the identity of Lasiodiplodia isolates was determined. The isolate CHES-21-DFCA was identified as Lasiodiplodia iraniensis (syn: L. iranensis) and the remaining three isolates, namely CHES-22-DFCA-1, CHES-22-DFCA-2, and CHES-22-DFCA-3, as L. theobromae. Although pathogenicity studies confirmed both L. iraniensis and L. theobromae were responsible for stem rot in dragon fruit, L. iraniensis was more virulent than L. theobromae. This study established the association of Lasiodiplodia species with stem rot in dragon fruit using a polyphasic approach. Further investigations are required, particularly related to on host-pathogen-weather interaction and spatiotemporal distribution across the major dragon fruit-growing areas of the country to formulate prospective disease management strategies. This is the first report on these two species of Lasiodiplodia inflicting stem rot in Hylocereus species in India.

Molecular Phylogeny, DNA Barcoding, and ITS2 Secondary Structure Predictions in the Medicinally Important Eryngium Genotypes of East Coast Region of India.

Commercial interest in the culinary herb, Eryngium foetidum L., has increased worldwide due to its typical pungency, similar to coriander or cilantro, with immense pharmaceutical components. The molecular delimitation and taxonomic classification of this lesser-known medicinal plant are restricted to conventional phenotyping and DNA-based marker evaluation, which hinders accurate identification, genetic conservation, and safe utilization. This study focused on species discrimination using DNA sequencing with chloroplast-plastid genes (matK, Kim matK, and rbcL) and the nuclear ITS2 gene in two Eryngium genotypes collected from the east coast region of India. The results revealed that matK discriminated between two genotypes, however, Kim matK, rbcL, and ITS2 identified these genotypes as E. foetidum. The ribosomal nuclear ITS2 region exhibited significant inter- and intra-specific divergence, depicted in the DNA barcodes and the secondary structures derived based on the minimum free energy. Although the efficiency of matK genes is better in species discrimination, ITS2 demonstrated polyphyletic phylogeny, and could be used as a reliable marker for genetic divergence studies understanding the mechanisms of RNA molecules. The results of this study provide insights into the scientific basis of species identification, genetic conservation, and safe utilization of this important medicinal plant species.

Discovery of potential 1,3,5-Triazine compounds against strains of Plasmodium falciparum using supervised machine learning models.

The Malaria burden was an escalating global encumbrance and need to be addressed with critical care. Anti-malarial drug discovery was integrated with supervised machine learning (ML) models to identify potent thiazolyl-traizine derivatives. This assimilated approach of Direct Kernel-based Partial Least Squares regression (DKPLS) with molprint 2D fingerprints in Quantitative Structure Activity Relationship models was utilized to map the knowledge of known actives and to design novel molecules. This QSAR study had revealed the structural features required for better antimalarial activity. Two of the molecules which were designed based on the results of this QSAR study, had shown good percentage of parasitemia against both chloroquine sensitive (3D7) and chloroquine resistant (Dd2) strains of Plasmodium falciparum respectively. The IC50 of 201D and 204D was 3.02 and 2.17 µM against chloroquine resistant Dd2 strain of Plasmodium falciparum. This result had proved the efficiency of a multidisciplinary approach of medicinal chemistry and machine learning for the design of novel potent anti-malarial compounds.

In silico ADMET study, docking, synthesis and antimalarial evaluation of thiazole-1,3,5-triazine derivatives as Pf-DHFR inhibitor.

BACKGROUND: Plasmodium falciparum dihydrofolate reductase (Pf-DHFR) is an essential enzyme in the folate pathway and is an important target for antimalarial drug discovery. In this study a modern approach has been undertaken to identify new hits of thiazole-1,3,5-triazine derivatives as antimalarials targeting Pf-DHFR. METHODS: The library of 378 thiazole-1,3,5-triazines were designed and subjected to ADME analysis. The compounds having optimal ADME score, was then evaluated by docking against wild and mutant Pf-DHFR complex. The resultant compound after screening from above these two methods were synthesized, and assayed for in vitro antimalarial against chloroquine-sensitive (3D-7) and chloroquine resistant (Dd-2) strains of P. falciparum. RESULTS: Twenty compounds were identified from the dataset based on considerable AlogP98 vs. PSA_2D confidence ellipse, ADME filter and TOPKAT toxicity analysis. Majority of compounds showed interaction with Asp54, Arg59, Arg122 and Ile 164 in docking analysis. Entire set of tested derivatives exhibited considerable activity at the tested dose against sensitive strain with IC50 values varying from 10.03 to 54.58 µg/ml. Furthermore, against chloroquine resistant strain, eight compounds showed IC50 from 11.29 to 40.92 µg/ml. Compound A5 and H16 were found to be the most potent against both the strains of P. Falciparum. CONCLUSION: Results of the study suggested the possible utility of thiazole-1,3,5-triazines as new lead for identifying new class of Pf-DHFR inhibitor.

Design, synthesis and antimalarial screening of some hybrid 4-aminoquinoline-triazine derivatives against pf-DHFR-TS.

Existing antifolate antimalarial drugs have shown resistance due to the mutations at some amino acid positions of Plasmodium falciparum DHFR-TS. In the present study, to overcome this resistance, a new series of hybrid 4-aminoquinoline-triazine derivatives were designed and docked into the active site of Pf-DHFR-TS (PDB i.d. 1J3K) using validated CDOCKER protocol. Binding energy was calculated by applying CHARMm forcefield. Binding energy and the pattern of interaction of the docked compounds were analysed. Fifteen compounds were selected for synthesis based on their binding energy values and docking poses. Synthesized compounds were characterised by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy and were screened for antimalarial activity against 3D7 strain of Plasmodium falciparum.

Prevalence and Risk Factors of HIV Infection among Clients Attending ICTCs in Six Districts of Tamilnadu, South India.

Objective. To assess the HIV serostatus of clients attending integrated counseling and testing centres (ICTCs) in Tamilnadu, south India (excluding antenatal women and children), and to study its association with demographic, socioeconomic, and behavioral risk factors. Design. In a prospective observational study, we interviewed clients attending 170 ICTCs from six districts of Tamilnadu during 2007 utilizing a standard pretest assessment questionnaire. All the clients were tested for HIV with rapid test kits. Multiple logistic regression analysis was used to identify determinants of HIV infection. Results. Of 18329 clients counseled, 17958 (98%) were tested for HIV and 732 (4.1%; range 2.6 to 6.2%) were tested positive for HIV. Median age of clients was 30 years; 89% had never used condoms in their lives and 2% gave history of having received blood transfusion. In multivariate analysis HIV seropositivity was associated with HIV in the family (adjusted odds ratio) (AOR 11.6), history of having sex with sex workers (AOR 2.9), age ≥31 years (AOR 2.8); being married (AOR 2.5), previously tested for HIV (AOR 1.9), illiteracy (AOR 1.7), unemployment (AOR 1.5), and alcoholism (AOR 1.5). Conclusion. HIV seroprevalence being high in ICTC clients (varied from 2.6 to 6.2%), this group should also be included in routine programme monitoring of sero-positivity and risk factors for better understanding of the impact of the National AIDS Control Programme. This would help in evolving appropriate policies and strategies to reduce the spread of HIV infection.

Panel 2.10: reproductive, mental, and child health.

This is a summary of the presentations and discussion of Panel 2.10, Reproductive, Mental, and Child Health of the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO) in Phuket, Thailand, 04-06 May 2005. The topics discussed included issues related to reproductive, mental, and child health as pertain to the responses to the damage created by the Tsunami. It is presented in the following major sections: (1) background; (2) key issues; (3) discussion; and (4) recommendations. Key issues discussed included: (1) coordination/collaboration; (2) provision of services; and (3) raising awareness and advocacy.