Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement - A Potential Therapeutic Option for Inflammatory Disorders.

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.

Untargeted and temporal analysis of retinal lipidome in bacterial endophthalmitis.

Bacterial endophthalmitis is a blinding infectious disease typically acquired during ocular surgery. We previously reported significant alterations in retinal metabolism during Staphylococcus (S) aureus endophthalmitis. However, the changes in retinal lipid composition during endophthalmitis are unknown. Here, using a mouse model of S. aureus endophthalmitis and an untargeted lipidomic approach, we comprehensively analyzed temporal alterations in total lipids and oxylipin in retina. Our data showed a time-dependent increase in the levels of lipid classes, sphingolipids, glycerolipids, sterols, and non-esterified fatty acids, whereas levels of phospholipids decreased. Among lipid subclasses, phosphatidylcholine decreased over time. The oxylipin analysis revealed increased prostaglandin-E2, hydroxyeicosatetraenoic acids, docosahexaenoic acid, eicosapentaenoic acid, and α-linolenic acid. In-vitro studies using mouse bone marrow-derived macrophages showed increased lipid droplets and lipid-peroxide formation in response to S. aureus infection. Collectively, these findings suggest that S. aureus-infection alters the retinal lipid profile, which may contribute to the pathogenesis of bacterial endophthalmitis.

Salinity and exogenous H2 O2 improve gas exchange, osmoregulation, and antioxidant metabolism in quinoa under drought stress.

Climate change-induced concurrent drought and salinity stresses significantly threaten global crop yields, yet the physio-biochemical responses to combined stress in quinoa remain elusive. This study evaluated quinoa responses under four growth conditions: well-watered, drought stress, salt stress, and drought + salt stress with (15 mM) or without (0 mM) exogenous hydrogen peroxide (H2 O2 ) application. All examined stresses (alone or in combination) reduce quinoa growth and net photosynthesis, although salt stress was found to be less destructive than drought and combined stress. Strikingly, superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), stomatal conductance (gs ), photosynthetic rate (PN ), K+ uptake, shoot height, shoot fresh, and dry weight were increased by 46.1%, 22.2%, 101.6%, 12.9%, 12.1%, 22.4%, 7.1%, 14%, and 16.4%, respectively, under combined stress compared to drought alone. In addition, exogenous H2 O2 effectively improved gaseous exchange, osmolytes' accumulation, and antioxidant activity, resulting in reduced lipid peroxidation, which eventually led to higher plant growth under all coercive conditions. The principle component analysis (PCA) indicated a strong positive correlation between antioxidant enzymes and inorganic ions, which contributed efficiently to osmotic adjustment, particularly under conditions of salinity followed by combined stress. In short, in combination, salt stress has the potential to mitigate drought-induced injuries by promoting the absorption of inorganic solutes for osmoregulation in quinoa plants. Furthermore, exogenous application of H2 O2 could be opted to enhance quinoa performance to increase its tolerance mechanism against drought and salinity, even under combined stress.

Mpox Virus and its ocular surface manifestations.

The Mpox virus (MPXV) is the causative agent of human Mpox disease - a debilitating rash illness similar to smallpox. Although Clade I MPXV has remained endemic to West and Central Africa, Clade II MPXV has been responsible for many outbreaks worldwide. The most recent outbreak in 2022 resulted from the rapid spread of a new clade of MPXV, classified into Clade IIb - a distinct lineage from the previously circulating viral strains. The rapid spread and increased severity of Mpox disease by the Clade IIb strain have raised the serious public health imperative of better understanding the host and viral determinants during MPXV infection. In addition to typical skin rashes, including in the periorbital area, MPXV causes moderate to severe ophthalmic manifestations - most commonly, ocular surface complications (e.g., keratitis, conjunctivitis, blepharitis). While ocular manifestations of Clade I Mpox within the Congo basin have been well-reported, global incidence trends of ocular Mpox cases by Clade IIb are still emerging. Given the demonstrated ability of all MPXV strains to auto-inoculate ocular tissue, alongside the enhanced transmissibility of the Clade IIb virus, there is an urgent need to elucidate the mechanisms by which MPXV causes ocular anomalies. In this review, we discuss the viral and genomic structures of MPXV, the epidemiology, and pathology of systemic and ocular Mpox, as well as potential prophylactic and therapeutic interventions.

Cross-cultural ethnobotany of the Baltis and Shinas in the Kharmang district, Trans-Himalaya India-Pakistan border.

Human communities that inhabit the political borders live a transitional life, which is due to several socio-political and geo-climatic factors. The current cross-cultural ethnomedicinal study was conducted at the highly elevated Pakistan-India borders of the Western Himalayas in order to address the medicinal flora and folk knowledge of Balti and Shina communities. Ethnobotanical field surveys were conducted from May 2021 to September 2022. We used semi-structured interviews in order to collect the ethnomedicinal data. The collected data was analyzed using the relative frequency of the citations, use value, and Venn diagrams. A total of 140 interviews were conducted, which comprised of 90 (64.28%) Baltis and 50 (35.71%) Shinas. The interviews recorded 60 medicinal plant species that belong to 56 genera and 35 families. Asteraceae (5 spp.), Lamiaceae (5 spp.), and Apiaceae (4 spp.) were the families that were the most represented. These medicinally valued plants were being used for 55 health issues that are related to different body systems. Delphinium brunonianum, Thymus linearis, Hymenolaena candollei, Corydalis adiantifolia, and Seriphidium brevifolium were medicinal taxa with maximum RFCs and UV. The Baltis have comparatively more ethnomedicinal knowledge than the Shinas. The Baltis commonly used 22 (36.66%) species, which 34 (56.66%) were exclusive to the Baltis and 4 (6.66%) to the Shinas. Both ethnic groups collectively hold significant ethnobotanical knowledge that demands the preservation of risked folk knowledge, which is due to uncertain border situations, outmigration, and permeating allopathic drugs.

Assessment of knowledge, attitude, and practices regarding the relationship of obesity with diabetes among the general community of Pakistan.

This study sought to evaluate the influence of knowledge, attitude, and practices assessment on diabetes related to obesity in Pakistani society. Data was collected both through door to door and online survey approaches from 518 participants by using a pre-validated questionnaire. A total of 15.6% were underweight, 61.2% were normal weight, 17.2% were overweight and 5.8% were in obesity class I and 2.9% were classified as obesity class II. The co-occurrence of obesity and diabetes was 29% (n = 22) among diabetic individuals (n = 84). A majority of the residents (59.1%) were from cities. While 94% of the participants responded to what obesity was, 83.8% knew what diabetes was. Fast food, soft drinks, and mayonnaise were deemed to be healthy by 75.1% of the respondents. Obesity was viewed as a disease by 94.8%, a major health issue by 78.2%, and a weight-loss necessity by 44.6% of participants. Only 24.9% exercised every day, and 23.9% engaged in any physical activity daily. The majority of respondents (50.6%) never tried to lose weight and 23.2% ate junk food daily. The sociodemographic variables showed that the age ranges of 25-34 years (P < 0.001; OR 0.531), 45-54 years (P < 0.05; OR 0.527), and urban residency (P < 0.001; OR 0.128) had a significant association with knowledge. The factors of urban residency (P < 0.001; OR 3.996), being unmarried (P < 0.001; OR 1.95), and having an income of 51,000-70,000 (P < 0.001; OR 11.29) showed a very highly significant association with a good attitude regarding the relationship of obesity with diabetes (P < 0.05). Similarly, practices of the participants showed significant association with BMI range of 18.5-24.9 and 25-29.9 (P < 0.001). Our study revealed significant knowledge and understanding of the relationship between obesity with diabetes. However, it was observed that majority of respondents exhibited fundamental knowledge regarding obesity and diabetes, there was a notable absence of understanding regarding crucial elements, such as the significance of maintaining a healthy body weight, participating in physical activity, and implementing appropriate dietary strategies for weight control. We recognize the necessity for education initiatives and strongly encourage them to assist individuals in managing diabetes resulting from obesity.

Enhancing linezolid activity in the treatment of oral biofilms using novel chitosan microneedles with iontophoretic control.

This study aimed to prepare and assess active microneedle (MN) patches based on a novel biomaterial and their effective coupled (physical and electrical) transdermal delivery of a model drug (Linezoid). Modified MN patches (e.g. fabricated from Linezoid, boronated chitosan, polyvinyl alcohol and D-sorbitol) were engineered using a vacuum micromoulding method. Physicochemical, FTIR (Fourier transform infrared), in-silico, structural and thermal analysis of prepared formulations were conducted to ascertain MN quality, composition and integrity. In-vitro mechanical tests, membrane toxicity, drug release, antibiofilm, ex-vivo mucoadhesion, insertion and in-vivo antibiofilm studies were performed to further validate viability of the coupled system. Optimized MN patch formulation (CSHP3 - comprising of 3 % w/v boronated chitosan, 3.5 % w/v PVA and 10 % w/w D-sorbitol) exhibited sharp-tipped, equi-distant and uniform-surfaced micron-scaled projections with conforming physicochemical features. FTIR analysis confirmed modification (i.e., boronation) of chitosan and compatibility as well as interaction between CSHP3 constituents. In-silico analysis indicated non-covalent interactions between all formulation constituents. Moreover, boronated chitosan-mucin glycoprotein complex showed a stronger bonding (∼1.86 times higher CScore) as compared to linezolid-mucin counterpart. Thermal analysis indicated amorphous nature of CSHP3. A âˆ¼ 1.42 times higher tensile strength was displayed by CSHP3 as compared to control (i.e., pure chitosan, polyvinyl alcohol and D-sorbitol-based MN patch). Membrane toxicity study indicated non-toxic and physiological compatible nature of CSHP3. Within 90 min, 91.99 ± 2.3 % linezolid was released from CSHP3. During release study on agarose gel, CSHP3-iontophoresis treatment resulted in a âˆ¼ 1.78 and âˆ¼ 1.20 times higher methylene blue-covered area and optical density, respectively, within 60 min as compared to CSHP3 treatment alone. Staphylococcus aureus biofilms treated with CSHP3 exhibited 65 ± 4.2 % reduction in their mass. CSHP3 MN patches remained adhered to the rabbit oral mucosa for 6 ± 0.15 h. Mucosa treated with CSHP3 and CSHP3-iontophoresis combination showed a generation of pathways in the epithelium layers without any damage to the underlying lamina propria. Eradication of Staphylococcus aureus from oral mucosal wounds and complete tissue regeneration was recorded following 7-day treatment using CSHP3-iontophoresis coupled approach.

Investigation of the role of Cremophor RH 40 and Cremophor EL in the inhibition of efflux pump of Pseudomonas aeruginosa.

Background: There is increasing emphasis on restoring the efficacy of existing antibiotics instead of developing new ones. Objectives: This study aimed to determine the role of Cremophor EL and Cremophor RH40 in the inhibition of efflux pumps in MDR Pseudomonas aeruginosa strains. Methods: Efflux pump-active MDR strains of P. aeruginosa were identified and confirmed by flow cytometry. The identified efflux-active strains were further subjected to determination of the MIC of ciprofloxacin and the synergistic role of non-ionic surfactants (Cremophor EL and Cremophor RH40) along with ciprofloxacin. Results: Out of 30 samples, 6 strains displayed high efflux pump activity. Both Cremophor EL and Cremophor RH40 showed efflux pump inhibitory roles. A 4-fold reduction in the MIC values of ciprofloxacin was observed when Cremophor EL was used along with ciprofloxacin, while a 6-fold reduction was observed when Cremophor RH40 was used along with ciprofloxacin. Both compounds showed synergistic effects with ciprofloxacin, ticarcillin and meropenem when used in a 24-well plate efflux pump inhibitory assay. Conclusion: The inhibition of the efflux pump of MDR Pseudomonas aeruginosa by non-ionic surfactants, namely, Cremophor RH40 and Cremophor EL, provided the best strategy to restore the efficacy of ciprofloxacin.

Antimicrobial activity of comfort related properties of silk treated with herbal extracts in making of reusable masks

The study was aimed at divulging an eco-friendly antimicrobial finish on 100 % silk woven fabric. The leaves' extract of Azadirachata indica, Butea monosperma and Litche chinensis were used as the development of eco-friendly antimicrobial finish. The antimicrobial property and comfort related property were checked before and after applying antimicrobial finish. In comfort related property absorbency & air permeability were checked. The ASTEM E2149 Shake Flask method was used to check antimicrobial finish and AATCC method was used for checking fabric property. One way ANOVA statistical test was applied for analysis of results. The FTIR and SEM results showed the presences of finish on fabrics. In comfort related property, absorbency and air permeability was increased. The results showed that antimicrobial finish made 100% reduction against microorganism up to 25 washes which can be used in making reusable masks fight against COVID- 19.