Ayurvedic herbal formulations Haridra Khanda and Manjisthadi Kwath (brihat) in the management of allergic rhinitis: A pharmacological study.

This study aims to pharmacologically validate Haridra Khanda (HK) and Manjishthadi Kwatham (brihat) (MMK) in allergy management using invivo and invitro studies to rationalize the prescription of these two ayurvedic polyherbal drug formulations, which are currently used in Indian government hospitals. Experimental animals received HK and MMK orally from day 0 to day 14 and histamine (1 mg/kg b.w/i.v) and 1 % evans blue (EB) (0.1 mL) via tail vein on day 14. The compound 48/80 (intracutaneous) challenged mice model followed the same technique. The former mimicked acute anaphylaxis and the latter mast cell degranulation. For both models, EB dye leakage was quantified spectrophotometrically to determine vascular permeability. Plasma histamine was measured in Compound 48/80-induced animals using LC-ESI-MS/MS. The guineapig received HK and MMK p.o. and 0.6 % histamine sprayed in a histamine chamber to simulate allergic rhinitis. Blood eosinophil count and sneeze rate were measured in histamine-challenged guineapigs. Goat R.B.C. membrane stability assay (mammalian cell membrane toxicity) and intracellular histamine-induced cytosolic Ca2+ release assay in Chinese hamster ovary (CHO) cells were performed in vitro. For both histamine and Compound 48/80 challenged animals, HK (22.81 % and 14.58 %) and MMK (19.71 % and 22.40 %) significantly reduced EB dye leakage (p < 0.05). Both formulations, HK and MMK considerably (p < 0.05) decreased plasma histamine (29.62 % and 25.37 % respectively) in mice and eosinophilic count (11.56 % and 9.94 % respectively) and sneeze rate (42.58 % and 29.03 % respectively) in guinea pigs. In membrane stability experiment, HK and MMK reduced RBC lysis. Both HK and MMK raw/dialysate blocked CHO cell cytosolic Ca2+ release. HK and MMK activities mimic mast cell stabilization with possible H1 receptor inactivation seen by decreased Ca2+ efflux and thus indicate potential for allergic rhinitis management. The combination of activities is usually related with curative and prophylactic therapy and might lead future clinical trials and therapies.

Simvastatin-Encapsulated Topical Liposomal Gel for Augmented Wound Healing: Optimization Using the Box-Behnken Model, Evaluations, and In Vivo Studies.

Statins function beyond regulating cholesterol and, when administered systemically, can promote wound healing. However, studies have yet to explore the topical use of statins for wound healing. The present study demonstrated the topical administration of SIM and aimed to formulate, evaluate, and optimize Simvastatin (SIM)-encapsulated liposome gel carrier systems to facilitate successful topical wound healing. Liposomes containing SIM were formulated and optimized via a response surface methodology (RSM) using the thin-film hydration method. The effects of formulation variables, including the 1,2-dioleoyloxy-3-trimethylammoniumpropan (DOTAP) concentration, Span 80 concentration, and cholesterol concentration, on zeta potential (mV), entrapment efficacy (%), and particle size (nm) were studied. The optimized liposome formulation (F-07) exhibited a zeta potential value of 16.56 ± 2.51 mV, revealing robust stability and a high SIM encapsulation efficiency of 95.6 ± 4.2%, whereas its particle size of 190.3 ± 3.3 nm confirmed its stability and structural integrity. The optimized liposome gel demonstrated pseudoplastic flow behavior. This property is advantageous in topical drug delivery systems because of its ease of application, improved spreadability, and enhanced penetration, demonstrating prolonged SIM release. The assessment of the wound healing efficacy of the optimized liposomal gel formulation demonstrated a substantial decrease in wound size in mice on the sixteenth day post-wounding. These findings suggest that the use of liposomal gels is a potential drug delivery strategy for incorporating SIM, thereby augmenting its effectiveness in promoting wound healing.

Box-Behnken Design-Based Optimization and Evaluation of Lipid-Based Nano Drug Delivery System for Brain Targeting of Bromocriptine.

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson's disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD.

Exploring the multimodal health-promoting properties of resveratrol: A comprehensive review.

Resveratrol, a natural polyphenol in various plants, has gained significant attention for its potential health-promoting properties. It has been demonstrated, after reviewing various clinical and in vitro studies, that resveratrol possesses potent antioxidant potential. Resveratrol demonstrates cellular component protection by directly neutralizing free radicals (FRs) and enhancing the expression of natural antioxidant enzymes, thereby mitigating oxidative damage to proteins, lipids, and nucleic acids. Clinical trials have shown promising results, indicating that resveratrol supplementation can enhance antioxidant defenses and reduce oxidative damage markers in various populations. In addition to its antioxidant effects, resveratrol exhibits potent anti-inflammatory properties. It can modulate key inflammatory pathways, such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), thereby suppressing the production of pro-inflammatory cytokines and chemokines. Furthermore, resveratrol's multimodal effects extend beyond its antioxidant and anti-inflammatory properties. It has been discovered to exert regulatory effects on various cellular processes, including apoptosis, cell cycle progression, angiogenesis, and immunological responses. The primary aim of this review paper is to provide a thorough overview of the current knowledge on resveratrol, including its chemical composition, bioaccessibility, clinical effectiveness, and utilization in nanotechnology to enhance its bioavailability. From future perspectives, revising the administration methods for certain contexts and understanding the underlying systems responsible for resveratrol's effects will require further inquiry. For the highest potential health results, advanced trial-based research is necessary for combinational nano-delivery of resveratrol.

ImSpect: Image-driven self-supervised learning for surgical margin evaluation with mass spectrometry.

PURPOSE: Real-time assessment of surgical margins is critical for favorable outcomes in cancer patients. The iKnife is a mass spectrometry device that has demonstrated potential for margin detection in cancer surgery. Previous studies have shown that using deep learning on iKnife data can facilitate real-time tissue characterization. However, none of the existing literature on the iKnife facilitate the use of publicly available, state-of-the-art pretrained networks or datasets that have been used in computer vision and other domains. METHODS: In a new framework we call ImSpect, we convert 1D iKnife data, captured during basal cell carcinoma (BCC) surgery, into 2D images in order to capitalize on state-of-the-art image classification networks. We also use self-supervision to leverage large amounts of unlabeled, intraoperative data to accommodate the data requirements of these networks. RESULTS: Through extensive ablation studies, we show that we can surpass previous benchmarks of margin evaluation in BCC surgery using iKnife data, achieving an area under the receiver operating characteristic curve (AUC) of 81%. We also depict the attention maps of the developed DL models to evaluate the biological relevance of the embedding space CONCLUSIONS: We propose a new method for characterizing tissue at the surgical margins, using mass spectrometry data from cancer surgery.

Comparative Safety and Efficacy of Low/Moderate-Intensity Statin plus Ezetimibe Combination Therapy vs. High-Intensity Statin Monotherapy in Patients with Atherosclerotic Cardiovascular Disease: An Updated Meta-Analysis.

AIM: Statin therapy is considered the gold standard for treating hypercholesterolemia. This updated meta-analysis aims to compare the efficacy and safety of a low/moderate-intensity statin in combination with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: A systematic search of two databases (PubMed and Cochrane CENTRAL) was conducted from inception to January 2023 and a total of 21 randomized clinical trials (RCTs) were identified and included in the analysis. Data were pooled using Hedges's g and a Mantel-Haenszel random-effects model to derive standard mean differences (SMDs) and 95% confidence intervals (Cis). The primary outcome studied was the effect of these treatments on lipid parameters and safety events. RESULTS: The results revealed that combination therapy was more effective in reducing low-density lipoprotein cholesterol (LDL-C) levels (SMD= - 0.41; CI - 0.63 to - 0.19; P = 0.0002). There was no significant change in the levels of high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP), Apo A1, or Apo B. The safety of these treatments was assessed by the following markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine phosphokinase (CK), and a significant difference was only observed in CK (SMD: - 0.81; CI - 1.52 to - 0.10; P = 0.02). CONCLUSION: This meta-analysis demonstrated that the use of low/moderate-intensity statin combination therapy significantly reduced LDL-C levels compared with high-intensity statin monotherapy, making it preferable for patients with related risks. However, further trials are encouraged to evaluate potential adverse effects associated with combined therapy.

Differential Use of Glycoprotein IIb/IIIa Inhibitors with Bivalirudin in Patients with STEMI Undergoing PCI: A Systematic Review and Meta-Analysis.

AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.

Effect of hesperidin on blood pressure and lipid profile: A systematic review and meta-analysis of randomized controlled trials.

The cardioprotective activity of hesperidin has been well demonstrated in several clinical studies. Also, there is a meta-analysis published on this topic in 2019. However, considering the recently published clinical studies, there is a scope for performing a systematic review and meta-analysis of hesperidin to determine its beneficial effect in alleviating alterations in cardiovascular parameters. In this study, the literature search was performed using online databases such as PubMed and Google Scholar till April 2023 involving randomized controlled studies conducted on hesperidin against various cardiovascular disorders including metabolic disorders in healthy/diseased individuals compared to the placebo/control. Based on the inclusion and exclusion criteria, nine clinical studies involving 2414 subjects were included. The meta-analysis revealed that hesperidin has significantly reduced the low-density lipoprotein (LDL) (IV: -0.55 (-0.94 to -0.16) at 95% CI, p = 0.005, I2 = 70%), total cholesterol (TC) (IV: -61 (-0.82 to -0.41) at 95% CI, p < 0.00001, I2 = 69%), and triglycerides (TG) (IV: -0.21 (-0.40 to -0.02) at 95% CI, p = 0.03, I2 = 12%). However, there were no statistically significant changes in the systolic blood pressure (IV: -0.29 (-2.21 to 1.63) at 95% CI, p = 0.77, I2 = 60%), diastolic blood pressure (IV: 0.79 (-0.74 to 2.31) at 95% CI, p = 0.31, I2 = 49%), and high-density lipoprotein (IV: 0.04 (-0.25 to 0.34) at 95% CI, p = 0.78, I2 = 56%) in the hesperidin treatment compared to the placebo/control. In conclusion, the outcomes of this meta-analysis suggest that hesperidin administration could benefit patients with CVD by reducing LDL, TC, and TG. Further high-quality studies are needed to firmly establish the clinical efficacy of hesperidin for its benefits in treating cardiovascular conditions.

Exploring the serotonin-probiotics-gut health axis: A review of current evidence and potential mechanisms.

Modulatory effects of serotonin (5-Hydroxytryptamine [5-HT]) have been seen in hepatic, neurological/psychiatric, and gastrointestinal (GI) disorders. Probiotics are live microorganisms that confer health benefits to their host. Recent research has suggested that probiotics can promote serotonin signaling, a crucial pathway in the regulation of mood, cognition, and other physiological processes. Reviewing the literature, we find that peripheral serotonin increases nutrient uptake and storage, regulates the composition of the gut microbiota, and is involved in mediating neuronal disorders. This review explores the mechanisms underlying the probiotic-mediated increase in serotonin signaling, highlighting the role of gut microbiota in the regulation of serotonin production and the modulation of neurotransmitter receptors. Additionally, this review discusses the potential clinical implications of probiotics as a therapeutic strategy for disorders associated with altered serotonin signaling, such as GI and neurological disorders. Overall, this review demonstrates the potential of probiotics as a promising avenue for the treatment of serotonin-related disorders and signaling of serotonin.

Quality by design aided self-nano emulsifying drug delivery systems development for the oral delivery of Benidipine: Improvement of biopharmaceutical performance.

The primary objective of the research effort is to establish efficient solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for benidipine (BD) through the systematic application of a quality-by-design (QbD)-based paradigm. Utilizing Labrafil M 2125 CS, Kolliphor EL, and Transcutol P, the BD-S-SNEDDS were created. The central composite design was adopted to optimize numerous components. Zeta potential, drug concentration, resistance to dilution, pH, refractive index, viscosity, thermodynamic stability, and cloud point were further investigated in the most efficient formulation, BD14, which had a globule size of 156.20 ± 2.40 nm, PDI of 0.25, zeta potential of -17.36 ± 0.18 mV, self-emulsification time of 65.21 ± 1.95 s, % transmittance of 99.80 ± 0.70%, and drug release of 92.65 ± 1.70% at 15 min. S-SNEDDS were formulated using the adsorption process and investigated via Fourier transform infrared spectroscopy, Differential scanning calorimeter, Scanning electron microscopy, and powder X-ray diffraction. Optimized S-SNEDDS batch BD14 dramatically decreased blood pressure in rats in contrast to the pure drug and the commercial product, according to a pharmacodynamics investigation. Accelerated stability tests validated the product's stability. Therefore, the development of oral S-SNEDDS of BD may be advantageous for raising BD's water solubility and expanding their releasing capabilities, thereby boosting oral absorption.

Corrigendum: Modulation of immune response by nanoparticle-based immunotherapy against food allergens.

[This corrects the article DOI: 10.3389/fimmu.2023.1229667.].

Preparation and characterization of a curcumin nanoemulsion gel for the effective treatment of mycoses.

Fungal infections of skin including mycoses are one of the most common infections in skin or skins. Mycosis is caused by dermatophytes, non-dermatophyte moulds and yeasts. Various studies show different drugs to treat mycoses, yet there is need to treat it with applied drugs delivery. This study was designed to prepare a bio curcumin (CMN) nanoemulsion (CMN-NEs) for transdermal administration to treat mycoses. The self-nanoemulsification approach was used to prepare a nanoemulsion (NE), utilizing an oil phase consisting of Cremophor EL 100 (Cre EL), glyceryl monooleate (GMO), and polyethylene glycol 5000 (PEG 5000). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), Fourier transform infrared (FTIR) spectrophotometric analysis, and morphological analyses were performed to evaluate the nanoemulsion (NE). The in vitro permeation of CMN was investigated using a modified vertical diffusion cell with an activated dialysis membrane bag. Among all the formulations, a stable, spontaneously produced nanoemulsion was determined with 250 mg of CMN loaded with 10 g of the oil phase. The average droplet size, ZP, and PDI of CMN-NEs were 90.0 ± 2.1 nm, - 7.4 ± 0.4, and 0.171 ± 0.03 mV, respectively. The release kinetics of CMN differed from zero order with a Higuchi release profile as a result of nanoemulsification, which also significantly increased the flux of CMN permeating from the hydrophilic matrix gel. Overall, the prepared nanoemulsion system not only increased the permeability of CMN but also protected it against chemical deterioration. Both CMN-ME (24.0 ± 0.31 mm) and CMN-NE gel (29.6 ± 0.25 mm) had zones of inhibition against Candida albicans that were significantly larger than those of marketed Itrostred gel (21.5 ± 0.34 mm). The prepared CMN-NE improved the bioavailability, better skin penetration, and the CMN-NE gel enhanced the release of CMN from the gel matrix on mycotic patients.

Development and Evaluation of Solid Dispersion-Based Sublingual Films of Nisoldipine.

Nisoldipine (NIS) is a calcium channel blocker that exhibits poor bioavailability (~5%) due to low aqueous solubility and presystemic metabolism in the gut wall. In this context, the present work aimed to develop NIS solid dispersion (NISSD)-based sublingual films using solvent casting technique to improve the dissolution. Phase solubility studies indicated that Soluplus® was the most effective carrier for improving the aqueous solubility of NIS. NISSDs were initially developed using the solvent evaporation method. Fourier transform infrared spectrometric studies were found to display the characteristic vibrational bands related to C=O stretching and N-H deformation in NISSDs, proving the chemical integrity of the drug in NISSDs. Subsequently, bioadhesive sublingual films of NISSDs were formulated using solvent casting method, using hydroxypropyl methyl cellulose (HPMC) E5, E15, and hydroxy ethyl cellulose (HEC EF) as hydrophilic polymers and polyethylene glycol 400 (PEG 400) as plasticizer. The incorporation of NISSDs was found to produce clear films that displayed uniform content. The sublingual film of NISSDs composed of HPMC E5 (2% w/v), was found to display the least thickness (0.29 ± 0.02 mm), the highest folding endurance (168.66 ± 4.50 times), and good bioadhesion strength (12.73 ± 0.503 g/cm2). This film was found to rapidly disintegrate (28.66 ± 3.05 sec) and display near-complete drug release (94.24 ± 1.22) in 30 min. Incorporating NISSDs into rapidly bioadhesive sublingual films considerably improves drug dissolution. Overall, these research outcomes underscored the potential of rapidly dissolving bioadhesive sublingual films to evade gut metabolism and resolve the bioavailability issues associated with oral administration of NIS.

Synergistic Antihyperglycemic and Antihyperlipidemic Effect of Polyherbal and Allopolyherbal Formulation.

Polyherbal formulation (PHF) enhances therapeutic efficacy and minimizes side effects by reducing individual herb dosages. Allopolyherbal formulation (APHF) combines polyherbal extracts with allopathic medication, effectively reducing the latter's required dose and mitigating associated adverse effects. The current study intends to assess the anti-diabetic effects of PHF and APHF in-vivo. Dried raw powders of Cassia auriculata leaf, Centella asiatica leaf, and Zingiber officinale rhizome were extracted by cold maceration process using 70% ethanol. These extracts were combined in three different ratios to make PHF. PHF was subjected to qualitative and quantitative phytochemical investigations. APHF has been prepared by combining a potent ratio of PHF with metformin in three different ratios. The compatibility of APHF has been confirmed by differential scanning calorimetry (DSC). In vivo activity was also evaluated in streptozotocin-induced diabetic albino rats. PHF (3 different ratios at a dose of 200-400 mg/kg b.w), APHF (combination of PHF and metformin in 3 different ratios, 200 + 22.5, 200 + 45, and 200 + 67.5 mg/kg b.w), and metformin (90 mg/kg b.w) were administered to albino rats for 21 consecutive days. Blood glucose levels were estimated on the 1st, 7th, 14th, and 21st days of treatment. On the 21st day, blood was collected by cardiac puncture for biochemical analysis. The liver and pancreas were isolated and subjected to histopathological analysis. PHF and APHF showed significant anti-diabetic and antihyperlipidemic efficacy. In comparison to PHF, APHF had the most promising action. The current study demonstrated that PHF and APHF are safe and efficacious drugs in the treatment of diabetes mellitus as they help to replace or lower the dose of metformin, thereby decreasing the risks of metformin.

Subconjunctival Delivery of Sorafenib-Tosylate-Loaded Cubosomes for Facilitated Diabetic Retinopathy Treatment: Formulation Development, Evaluation, Pharmacokinetic and Pharmacodynamic (PKPD) Studies.

Diabetic retinopathy (DR) is a microvascular complication associated with vascular endothelial growth factor (VEGF) overexpression. Therapeutic delivery to the retina is a challenging phenomenon due to ocular biological barriers. Sorafenib tosylate (ST) is a lipophilic drug with low molecular weight, making it ineffective at bypassing the blood-retinal barrier (BRB) to reach the target site. Cubosomes are potential nanocarriers for encapsulating and releasing such drugs in a sustained manner. The present research aimed to compare the effects of sorafenib-tosylate-loaded cubosome nanocarriers (ST-CUBs) and a sorafenib tosylate suspension (ST-Suspension) via subconjunctival route in an experimental DR model. In this research, ST-CUBs were prepared using the melt dispersion emulsification technique. The distribution of prepared nanoparticles into the posterior eye segments was studied with confocal microscopy. The ST-CUBs were introduced into rats' left eye via subconjunctival injection (SCJ) and compared with ST-Suspension to estimate the single-dose pharmacokinetic profile. Streptozotocin (STZ)-induced diabetic albino rats were treated with ST-CUBs and ST-Suspension through the SCJ route once a week for 28 days to measure the inhibitory effect of ST on the diabetic retina using histopathology and immunohistochemistry (IHC) examinations. Confocal microscopy and pharmacokinetic studies showed an improved concentration of ST from ST-CUBs in the retina. In the DR model, ST-CUB treatment using the SCJ route exhibited decreased expression levels of VEGF, pro-inflammatory cytokines, and adhesion molecules compared to ST-Suspension. From the noted research findings, it was concluded that the CUBs potentially enhanced the ST bioavailability. The study outcomes established that the developed nanocarriers were ideal for delivering the ST-CUBs via the SCJ route to target the retina for facilitated DR management.

Modulation of immune response by nanoparticle-based immunotherapy against food allergens.

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.

Implications of Pharmacokinetic Potentials of Pioglitazone Enantiomers in Rat Plasma Mediated through Glucose Uptake Assay.

Pioglitazone, a PPAR-gamma activator used to diagnose hyperglycemia, was studied for its stereoselective deposition and active enantiomers in female albino Wistar rats. In accordance with USFDA recommendations, a bioanalytical technique was employed to assess the segregation of pioglitazone enantiomers in rat plasma with glimepiride as an internal standard. A Phenomenox i-Amylose-3 column (150 mm × 4.6 mm) of 5 µm was used for high-performance liquid chromatography (HPLC) with a mobile phase of 10 mM ammonium acetate buffer in Millipore water and acetonitrile in 60:40 (v/v) admixture with column temperature 35 °C, wavelength 265 nm, and flow rate 0.6 mL/min, respectively. Pioglitazone-S, Pioglitazone-R, and the internal standard had retention times of 3.1, 7.4, and 1.7 min, respectively. The study found that within-run and between-run precision ranged from 0.1606-0.9889% for Pioglitazone-R and from 0.2080-0.7919% for Pioglitazone-S, while the accuracy ranged from 99.86 to 100.36% for Pioglitazone-R and 99.84 to 99.94% for Pioglitazone-S. In addition, a non-radioactive glucose uptake assay was employed to examine the enantiomers in 3T3-L1 cell lines by flow cytometry. Significant differences were demonstrated in Cmax, AUClast (h*µg/mL), AUCINF obs (h*µg/mL), and AUC%Extrap obs (%) of Pioglitazone-R and S in female albino Wistar rats, suggesting enantioselectivity of pioglitazone.

Trajectory of COVID-19 vaccine hesitancy post-vaccination and public's intention to take booster vaccines: A cross-sectional analysis.

Vaccine hesitancy (VH) is not a new phenomenon in Pakistan and is regarded as one of the primary causes of unsatisfactory vaccination campaigns. This study determined post-vaccination COVID-19 VH, factors influencing COVID-19 vaccine uptake, and public's intent to receive booster vaccinations. A cross-sectional study was conducted among adult population of Lahore, Pakistan. Participants were recruited via convenience sampling between March and May 2022. SPSS version 22 was used for the data analysis. A total of 650 participants were included in the study (age = 28.1 ± 9.7 years; male-to-female ratio nearly 1: 1). The majority of participants received Sinopharm followed by Sinovac vaccine. The top three reasons of vaccine uptake were "only vaccinated individuals are allowed at the workplace, and educational institutes" (Relative importance index (RII) = 0.749), "only vaccinated people are allowed to go to markets, malls and other public places" (RII = 0.746), and "protect myself from the infection" (RII = 0.742). The mean COVID-19 VH score was 24.5 ± 6.2 (95% CI 23.9-24.9), with not being pro-vaccines and poor economic status were the significant predictors of COVID-19 vaccine hesitancy among immunized individuals (p < .05). Acceptance of booster vaccines was negatively associated with younger age and a lower level of education. Furthermore, being pro-vaccine was associated with a greater likelihood of accepting booster vaccines (p = .001). The Pakistani public continues to express VH toward COVID-19 vaccines. Therefore, aggressive measures must be taken to combat the community factors that contribute to it.

Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment.

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology.