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The experiment was designed to evaluate the consequence of a blend of garlic oil and cinnamon bark powder administration on growth performance, nutrient digestibility, immunity, antioxidant status and methane emission in Murrah buffalo (Bubalus bubalis). Sixteen buffalo calves were divided into two groups in a completely randomised design. The first group (CONT) was fed a basal diet of wheat straw, green oats and concentrate mixture, whereas the second group (GOCB) received feeds as per the CONT along with a blend of garlic oil and cinnamon bark powder (0.5 mL + 1.0 g/head/day) by mixing it with the concentrate mixture for a period of 170 days. The growth rate and feed efficiency in GOCB group buffalo calves were improved (20%) with better (p < 0.05) digestibility of organic matter and crude proteins. Buffaloes of the GOCB group revealed enhanced (p < 0.05) immunity and antioxidant enzymes with reduced (p < 0.05) lipid peroxidation (26% less MDA production). The methane concentration in the eructed gas of the GOCB buffaloes was reduced (33.88%) in comparison with the CONT (p < 0.01). Thus, feed formulated with a blend of garlic oil-cinnamon bark powder demonstrates improvements in the health and production performances of buffalo calves.

Background Human face is complex and intricate structure, with several features that are unique to each individual and can be taken as an identity pass in this mortal world. The facial profile of an individual holds materialistic value and is crucial for human identification. Present study aims to investigate the influence of sex and age of an individual on the soft tissue thicknesses (FSTT) at midline facial landmarks estimated on MRI scans. Methods Facial soft tissue thickness was estimated at 20 midline landmarks on the MRI scans of 120 (57 male; 63 female) anatomically normal Northwest Indian adult subjects (18–70 + years age-group). Age and sex dependent variations in tissue thicknesses at different landmarks were estimated using statistical software IBM SPSS Statistics 23. Results The results of the study yielded that most of the midline landmarks had higher values in males than in females indicating observable sexual dimorphism in FSTT values in this facial region, statistically significant differences were also noted in soft tissue thickness estimates of different age-groups, showing increasing or decreasing trend with age. The mid-facial landmarks like mid-philtrum, supra-dentale, incisor superius, and labile inferius displayed highly significant p values. Conclusions Present study results were in tandem with the findings of previous studies; males and younger age-group individuals were having higher tissue thickness values than the females and older individuals, respectively. The highest soft tissue estimates were obtained for the middle age subjects and the most aged individuals had the least midline soft tissue thickness values. These results can have significant forensic anthropological repercussions in attempting facial approximations on unknown skulls and identification of unknown individuals from still images, photographs or videos.

Salmonella enterica serotype Typhi causes chronic enteric fever known as typhoid. Prolonged treatment regimen used for the treatment of typhoid and indiscriminate use of antibiotics has led to the emergence of resistant strains of S. enterica that has further increased the severity of the disease. Therefore, alternative therapeutic agents are urgently required. In this study, probiotic and enterocin-producing bacteria Enterococcus faecium Smr18 was compared for both its prophylactic and therapeutic efficacy in S. enterica infection mouse model. E. faecium Smr18 possessed high tolerance to bile salts and simulated gastric juice, as treatment for 3 and 2 h resulted in 0.5 and 0.23 log 10 reduction in the colony forming units, respectively. It exhibited 70% auto aggregation after 24 h of incubation and formed strong biofilms at both pH 5 and 7. Oral administration of E. faecium in BALB/c mice infected with S. enterica significantly ( p  < 0.05) reduced the mortality of the infected mice and prevented the weight loss in mice. Administration of E. faecium prior to infection inhibited the translocation of S. enterica to liver and spleen, whereas, its administration post-infection completely cleared the pathogen from the organs within 8 days. Further, in both pre- and post- E . faecium -treated infected groups, sera levels of liver enzymes were restored back to normal; whereas the levels of creatinine, urea and antioxidant enzymes were significantly ( p  < 0.05) reduced compared to the untreated-infected group. E. faecium Smr18 administration significantly increased the sera levels of nitrate by 1.63-fold and 3.22-fold in pre- and post-administration group, respectively. Sera levels of interferon-γ was highest (tenfold) in the untreated-infected group, whereas the levels of interleukin-10 was highest in the post-infection E. faecium- treated group thereby indicating the resolution of infection in the probiotic-treated group, plausibly due to the increased production of reactive nitrogen intermediates.

Background The present study focused on developing a superior adsorbent carrier (microparticles) to solidify the self-emulsifying drug delivery system. The two approaches, solvent evaporation and spray drying, were explored to synthesize the microparticles using chitosan (CH) and EDTA disodium. The 3 2 full factorial design was applied to optimize the microparticle process produced by both methods. Results The various characterization evaluations of the microparticles revealed amide linkages between the CH and EDTA disodium, and XRD results showed that microparticles were amorphous. The SE-CHEM (C 2 ) and SD-CHEM (Y 1 ) optimized microparticles were free-flowing and had percentage yield (%), 96 ± 1.2 and 58 ± 1.1, zeta potential (mV), 9 ± 0.44 and 4 ± 0.13, and particle size (μm), 3 ± 0.57 and 2 ± 0.4, respectively. SEM images showed uneven surfaces with wide void spaces and flaky texture for optimized microparticles Y 1 and C 2 , respectively. The SE-CHEM (C 2 ) had an oil adsorption capacity (OAC %) of 46 ± 0.54 and 60 ± 0.77, and oil desorption capacity (ODC %), 38 ± 0.65 and 56 ± 0.86, for Labrafac and Cremophor RH 40, respectively. The SD-CHEM (Y 1 ) had an oil adsorption capacity (OAC %) of 59 ± 0.71 and 68 ± 0.39, and oil desorption capacity (ODC %), 54 ± 0.11 and 65 ± 0.74, for Labrafac and Cremophor RH 40, respectively. In the surface free energy components analysis, the SE-CHEM (C 2 ) had an enhanced dispersive component [ γ LW (mJ/m 2 )] of 32 ± 0.68 and 37 ± 0.47 for Labrafac and Cremophor RH 40, respectively. The SD-CHEM (Y 1 ) had an enhanced dispersive component [ γ LW (mJ/m 2 )] of 48 ± 0.7 and 52 ± 0.41 for Labrafac and Cremophor RH 40, respectively. The SE-CHEM (C 2 ) had enhanced dynamic advancing contact angles [ θ a (°)] of 75 ± 0.19 and 78 ± 0.75 for Labrafac and Cremophor RH 40, respectively. The SD-CHEM (Y 1 ) had enhanced dynamic advancing contact angles [ θ a (°)] of 74 ± 0.6 and 80 ± 0.21 for Labrafac and Cremophor RH 40, respectively. Conclusion All the findings indicate that the microparticles have superior characteristics to serve as the adsorbent base for solid self-emulsifying drug delivery systems.

The potential for plant-origin essential oils to modulate rumen functions for reducing bio-hydrogenation of fatty acids and methane production has been a significant area of research in recent times. This study investigated the effects supplementation of garlic (Allium sativum) essential oils have on in vitro bio-hydrogenation of fatty acids, methanogenesis and fermentation characteristics of total mixed ration in buffalo with the aim of enhancing conjugated linoleic acid (CLA) content in animal products as well as reducing environmental pollution. Allium sativum (AS) essential oils were examined at four levels [0 (Control), 33.33 µL (AS-1), 83.33 µL (AS-2) and 166.66 µL (AS-3) per litre of buffered rumen fluid] in a radio-frequency based automatic gas production system (ANKOM-RF). Two bottles per treatment per run over two incubation runs were undertaken to gain representative results. Oats hay and concentrate mixture (1:1) was used as a substrate (500 ± 5 mg) and incubated with 60 mL of buffered rumen fluid in 250 mL ANKOM bottles fitted with automatic an gas recording system at 39 °C for 24 h, following standard in vitro gas production protocols. The results demonstrated a reduction (p < 0.01) in lipid bio-hydrogenation, measured by lowered saturated fatty acids and enhanced unsaturated fatty acids on the supplementation of AS essential oils, irrespective of the dose levels. Moreover, the increased (p < 0.01) production of trans vaccenic (trans C18:1) acid (TVA) following graded dose supplementations of the AS essential oils increased the production of conjugated linoleic acids (CLA) in animal products. Although, reduced methane production (p < 0.01) was evidenced, the decrease in total gas production and feed digestibility (TDDM) demonstrated the strong antimicrobial properties of AS at all dose levels. The study reveals that the Allium sativam (Garlic) essential oils have the potential to be an agent for the reduction of the rumen biohydrogenation of fatty acids and methanogenesis. However, in vivo examination is necessary to validate the findings and confirm its suitability for use as an additive to enhance nutraceutical and organoleptic properties in animal products.

Hypersensitivity reactions to complement activation-related pseudo-allergy (CARPA) pose a serious concern to patient safety when using nanoparticle-based drug delivery systems (NDDS). Complement activation-related pseudo-allergy is a severe, idiosyncratic hypersensitivity reaction consequent to complement activation and liberation of potent pro-inflammatory molecules. Recent developments have concentrated on identifying, managing, and preventing CARPA to improve the efficacy and safety of NDDS, including early identification biomarkers and highly sensitive diagnostic techniques. The development of biocompatible nanoparticles, surface changes to reduce complement activation, and the use of complement inhibitors are some of the innovative strategies for CARPA reduction that are highlighted. Furthermore, newly developed management procedures, such as premedication schedules, customized dosage plans, and real-time monitoring methods, are also covered. The scope of this review encompasses the new diagnostic methods based on in-vitro assays, ex-vivo models, and highly sensitive imaging techniques for the detection of complement activation and other related pseudo-allergic reactions including liposome encapsulation and PEGylation to enhance biocompatibility and decrease immune stimulation. Special emphasis is paid to the application of high-throughput screening technologies and omics tools that enhance the likelihood and evaluation of CARPA immunogenicity. Integration of these approaches forms a comprehensive approach to improving the understanding and administration of CARPA in clinical settings to increase patient safety during nanoparticle-based treatment. The advanced alignments complement regulatory and clinical concerns and connect experimental paradigms to applications, such integration of knowledge provides a platform for the development of next-generation NDDSs for reducing CARPA and enhancing the efficiency of medication delivery thereby increasing patient compliance. This abstract delineates the methods of diagnosing, preventing, and managing CARPA, with addressing the nanotechnology for the problem.

The development of effective therapy is necessary because the patients have to contend with long-term therapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certain shortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7 nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. The solubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug. Graphical Abstract

This study investigated the role of sodium bicarbonate in changing intermolecular hydrogen bonding to intramolecular hydrogen bonding within methyl cellulose (MC) to induce locoregional anticancer action of paclitaxel at physiological temperature. Simple thin-film hydration method was used to produce paclitaxel nanovesicles in commercial strength to impart in situ gelations. ATR-FTIR spectrometric evaluation showed compatibility between drug and excipients and DSC analysis revealed the conversion to intramolecular hydrogen bonding in MC-based formulation. Single-dose acute and 28 days sub-acute toxicity studies on mice displayed the safety of the optimized nanovesicular injectable formulation of paclitaxel. A pharmacokinetic study in mice plasma exhibited sustained drug levels from the optimized in situ nanovesicular formulation compared to the commercial formulation of paclitaxel. EAC induction in mice and treatment from the optimized thermosensitive in situ injectable formulation were observed to have better tumor control. Very poor aqueous solubility of paclitaxel was eliminated while exerting localized action with the novel MC-based thermosensitive in situ nanovesicular formulation in terms of in vitro depot formation, reduced toxicity, and better anticancer effect. Vital blood parameters and organs of mice under study were found to be normal with the effect of the optimized formulation treatment in comparison to commercial injectable of paclitaxel. Our findings revealed that sodium bicarbonate successfully brought the gelation point of MC from over 60 °C to below physiological temperature to impart stiffness in the injectable formulation of paclitaxel for locoregional effect. The efficacy of the developed formulation was confirmed through in vitro, ex vivo, and in vivo parameters. Graphical abstract Highlights Sodium bicarbonate lowered the gelation temperature of methyl cellulose injectable formulation for in situ gelation near-physiological temperature. Optimized formulation led to enhanced solubility of paclitaxel with localized action near the vicinity of ovarian tumor. Developed MC-based nanovesicles revealed in vitro sustained drug release profile, lower IC 50 values on cell lines, better plasma drug concentrations, and control of tumor in mice.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro , ex vivo , and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns. Graphical Abstract

Purpose A second-generation retinoid “acitretin” has been used to treat severe psoriatic conditions. The commercial formulation of acitretin comes exclusively in capsule form. Presently, no topical formulation of acitretin is available commercially; so in the present study, solid lipid nanoparticle (SLN)-based topical formulation was developed for sustained exposure of drug on affected areas along with reduction in systemic toxicity. Method SLNs were prepared by solvent injection method using solid lipid, phospholipid, and drug dissolved in the solvent, where the lipid phase was added to the aqueous phase. The developed formulation was loaded into the gel-based matrix for topical administration and extensive characterizations were performed in vitro, ex vivo, and in vivo. Result The optimized formulation F14 was found to have encapsulation efficiency of 89.86 ± 1.8% and required PDI of 0.488 with zeta potential of − 17.2 mV to denote stability. On rat skin, mice skin, and Strat-M membrane, the skin permeation study with the optimized formulation revealed enhancement ratios of 2.5, 2.4, and 2.2, respectively. The optimized gel formulation based on SLN had 1.75 times more drug penetration with even distribution into the skin layer, as determined by confocal laser scanning microscopy. When evaluated for drug deposition potential on rat, mice, and membrane Strat-M membrane, the optimized formulation exerted 3.62-, 4.35-, and 3.25-fold action. Conclusion The results demonstrated the developed SLN-based gel formulation to be an effective and safe tool in topical administration of acitretin with no skin irritation potential and higher skin deposition as well as an alternative to its oral route therapy.