Lipidic Nanosystem as State-of-the-Art Nanovehicle for Biomedical Applications.

Lipids have tremendously transformed the biomedical field, especially in the last few decades. Nanosystems, especially Lipid nanocapsules (LNCs), have emerged as the most demanding nanovehicle systems for delivering drugs, genes, and other diagnostic agents. Unique attributes and characteristic features such as higher encapsulation efficiency, stealth effect, ability to solubilize a wide range of drugs, capability to inhibit P-gp efflux pumps, and higher stability play a vital role in engaging this nanosystem. LNCs are a lipid-based nano-drug delivery method that combines the most significant traits of liposomes with polymeric nanoparticles. Structurally, LNCs have an oily core consisting of medium and long triglycerides and an aqueous phase encased in an amphiphilic shell. This manuscript crosstalks LNCs for various biomedical applications. A detailed elaboration of the structural composition, methods of preparation, and quality control aspects has also been attained, with particular emphasis on application approaches, ongoing challenges, and their possible resolution. The manuscript also expounds the preclinical data and discusses the patents atlas of LNCs to assist biomedical scientists working in this area and foster additional research. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01298-3.

Sustainable Consumption: Will They Buy It Again? Factors Influencing the Intention to Repurchase Organic Food Grain.

Global consumption trends point to rising demand for organic food as people become more health-conscious. The factors that people consider while making initial organic purchases have been discussed at length. However, the published research is scant about the factors that affect consumers' propensity to repurchase organic goods. The present research fills this gap by focusing on what influences consumers' decisions to repurchase organic grain. The Stimulus-Organism-Response (S-O-R) theory and the Theory of Planned Behaviour are the theoretical foundations of the present investigation. The consumer's attitude toward organic grains and their desire to repurchase organic grains are influenced by health consciousness and previous experience. The repurchase intent was determined to be controlled by the buyer's willingness to pay and their level of trust in the organic grain. This cross-sectional study collected the necessary data from five chosen urban centres in India. Smart PLS 3.2.9 was used to analyse the gathered data from 463 respondents. According to the findings, health consciousness and past experience favourably influence attitudes and repurchase intent. The trust that consumers have built up in organic grain as a result of past experiences is what drives their desire to make more purchases. Willingness to pay significantly controls and impacts the inclination to repurchase. The association between health consciousness and repurchase intention is partially mediated by attitude, as is the relationship between past experience and repurchase intention. The relationship between health consciousness and the desire to repurchase is partially mediated by the willingness to pay.

Strength of titanium-zirconium alloy implants with a conical connection after implantoplasty.

STATEMENT OF PROBLEM: Peri-implantitis occurs around dental implants, and implantoplasty has been used to address this ongoing disease; however, the changes to the physical properties of an implant after implantoplasty have not been well documented. PURPOSE: The purpose of this in vitro study was to determine the effect of implantoplasty on fracture strength and the load required for plastic deformation after cyclic fatigue on dental implants. MATERIAL AND METHODS: Twenty-six titanium/zirconium (TiZr) alloy implants (Roxolid Bone Level Implant; 4.1×10 mm) were embedded with 50% thread exposure and divided into 4 groups based on whether they had implantoplasty treatment by using different diamond rotary instruments and/or cyclic loading at 250 N for 2 million cycles: C0 (control, no cyclic loading), T0 (test, no cyclic loading), CM (control, cyclic loading), and TM (test, cyclic loading). After implantoplasty and/or cyclic loading, all implants underwent a load-to-failure test. The maximum fracture strength (FS) and load required for the onset of plastic deformation (PD) were recorded in Newtons. One-way ANOVA and nonparametric comparisons with control by using the Dunn and Wilcoxon method for joint ranking were used for statistical analysis. RESULTS: The mean ±standard deviation FS for C0, CM, T0, and TM was 1465.2 ±86.4 N, 1480.7 ±64.1 N, 1299.3 ±123.8 N, and 1252.1 ±85.7 N, respectively. The mean ±standard deviation load for onset of PD for C0, CM, T0, and TM was 860.2 ±88.1 N, 797.0 ±130.5 N, 776.5 ±181.8 N, and 631.3 ±84.5 N, respectively. The TM group had a significantly lower FS and PD than the C0, CM, and T0 groups (P<.05) CONCLUSIONS: Both fracture strength (FS) and the onset of plastic deformation (PD) were significantly reduced after a TiZr alloy implant received implantoplasty and cyclic loading.

PITPs as targets for selectively interfering with phosphoinositide signaling in cells.

Sec14-like phosphatidylinositol transfer proteins (PITPs) integrate diverse territories of intracellular lipid metabolism with stimulated phosphatidylinositol-4-phosphate production and are discriminating portals for interrogating phosphoinositide signaling. Yet, neither Sec14-like PITPs nor PITPs in general have been exploited as targets for chemical inhibition for such purposes. Herein, we validate what is to our knowledge the first small-molecule inhibitors (SMIs) of the yeast PITP Sec14. These SMIs are nitrophenyl(4-(2-methoxyphenyl)piperazin-1-yl)methanones (NPPMs) and are effective inhibitors in vitro and in vivo. We further establish that Sec14 is the sole essential NPPM target in yeast and that NPPMs exhibit exquisite targeting specificities for Sec14 (relative to related Sec14-like PITPs), propose a mechanism for how NPPMs exert their inhibitory effects and demonstrate that NPPMs exhibit exquisite pathway selectivity in inhibiting phosphoinositide signaling in cells. These data deliver proof of concept that PITP-directed SMIs offer new and generally applicable avenues for intervening with phosphoinositide signaling pathways with selectivities superior to those afforded by contemporary lipid kinase-directed strategies.

Resurrection of a functional phosphatidylinositol transfer protein from a pseudo-Sec14 scaffold by directed evolution.

Sec14-superfamily proteins integrate the lipid metabolome with phosphoinositide synthesis and signaling via primed presentation of phosphatidylinositol (PtdIns) to PtdIns kinases. Sec14 action as a PtdIns-presentation scaffold requires heterotypic exchange of phosphatidylcholine (PtdCho) for PtdIns, or vice versa, in a poorly understood progression of regulated conformational transitions. We identify mutations that confer Sec14-like activities to a functionally inert pseudo-Sec14 (Sfh1), which seemingly conserves all of the structural requirements for Sec14 function. Unexpectedly, the "activation" phenotype results from alteration of residues conserved between Sfh1 and Sec14. Using biochemical and biophysical, structural, and computational approaches, we find the activation mechanism reconfigures atomic interactions between amino acid side chains and internal water in an unusual hydrophilic microenvironment within the hydrophobic Sfh1 ligand-binding cavity. These altered dynamics reconstitute a functional "gating module" that propagates conformational energy from within the hydrophobic pocket to the helical unit that gates pocket access. The net effect is enhanced rates of phospholipid-cycling into and out of the Sfh1* hydrophobic pocket. Taken together, the directed evolution approach reveals an unexpectedly flexible functional engineering of a Sec14-like PtdIns transfer protein-an engineering invisible to standard bioinformatic, crystallographic, and rational mutagenesis approaches.

Zebrafish class 1 phosphatidylinositol transfer proteins: PITPbeta and double cone cell outer segment integrity in retina.

Phosphatidylinositol transfer proteins (PITPs) in yeast co-ordinate lipid metabolism with the activities of specific membrane trafficking pathways. The structurally unrelated metazoan PITPs (mPITPs), on the other hand, are an under-investigated class of proteins. It remains unclear what biological activities mPITPs discharge, and the mechanisms by which these proteins function are also not understood. The soluble class 1 mPITPs include the PITPalpha and PITPbeta isoforms. Of these, the beta-isoforms are particularly poorly characterized. Herein, we report the use of zebrafish as a model vertebrate for the study of class 1 mPITP biological function. Zebrafish express PITPalpha and PITPbeta-isoforms (Pitpna and Pitpnb, respectively) and a novel PITPbeta-like isoform (Pitpng). Pitpnb expression is particularly robust in double cone cells of the zebrafish retina. Morpholino-mediated protein knockdown experiments demonstrate Pitpnb activity is primarily required for biogenesis/maintenance of the double cone photoreceptor cell outer segments in the developing retina. By contrast, Pitpna activity is essential for successful navigation of early developmental programs. This study reports the initial description of the zebrafish class 1 mPITP family, and the first analysis of PITPbeta function in a vertebrate.

Escitalopram Versus Citalopram and Sertraline: A Double-Blind Controlled, Multi-centric Trial in Indian Patients with Unipolar Major Depression.

The present randomized, double blind, parallel group, controlled, multi-centric trial was designed to evaluate the efficacy and tolerability of escitalopram in comparison with citalopram and sertraline in the treatment of major depressive disorder. Outpatients (N=214) with an ongoing/newly diagnosed ICD-10 major depressive episode and a Hamilton Rating Scale for Depression (HAM-D) score of > 18 were randomly assigned to citalopram, 20-40 mg/day (74 patients), escitalopram, 10-20 mg/day (69 patients) and sertraline, 50-150 mg/day (71 patients), for a 4-week double-blind treatment period, with dosage adjustment (after 2 weeks of treatment) according to the response to treatment. Clinical response was evaluated by the 17 items HAM-D and the Clinical Global Impression (CGI) scales, which were recorded at baseline and at weekly intervals. Tolerability was evaluated by observed/spontaneously reported adverse changes in laboratory parameters (baseline and after 4 weeks). Response rate was defined as a decrease in HAM-D score by 50% from baseline and remission rate was defined as a HAM-D score of < 8. Response rate at the end of two week were 58% for escitalopram (10mg/day), 49% for citalopram (20mg/day) and 52% for sertraline (50-100mg/day). Response rate at the end of four week were 90% for escitalopram (10-20mg/day), 86% for citalopram (20-40mg/day) and 97% for sertraline (100-150mg/day). The Remission rates at the end of four weeks were 74% for escitalopram, 65% for citalopram and 77% for sertraline. Adverse experiences were reported by 45% of patients in escitalopram group, 58% patients in citalopram and 56% patients in the sertraline group. Additionally, there were lesser dropouts and lesser requirement for dose escalation in escitalopram than in citalopram and sertraline group. In conclusion Escitalopram, the Senantiomer of the citalopram is a safe and effective antidepressant in the Indian population. It has potentially superior efficacy than citalopram and a comparable efficacy to sertraline with fewer side effects than both citalopram and sertraline.