Greater Efficacy Research Articles

Encapsulation of Nanocrystals in Mannitol-Based Inhalable Microparticles via Spray-Drying: A Promising Strategy for Lung Delivery of Curcumin

Background/Objectives: Curcumin is well known for its great anti-inflammatory and antioxidant efficacy, representing a potential strategy for the treatment of respiratory disorders. However, several drawbacks, such as chemical instability, poor water solubility and rapid metabolism, result in low bioavailability, limiting its clinical applications. In this study, curcumin nanocrystals were incorporated into mannitol-based microparticles to obtain an inhalable dry powder. Methods: A curcumin nanosuspension was produced by wet-ball media milling and thoroughly characterized. Spray drying was then used to produce mannitol microparticles incorporating curcumin nanocrystals. In vitro release/dissolution tests were carried out in simulated lung fluids, and the aerosolization properties were evaluated using a Next-Generation Impactor (NGI, Apparatus E Ph. Eu.). Results: The incorporation of curcumin nanocrystals into mannitol-based microparticles influenced their morphological properties, such as geometric diameters, and flowability. Despite these changes, nebulization studies confirmed optimal MMAD values (<5 µm), while multi-step dissolution/release studies evidenced the influence of mannitol. Conclusions: The developed curcumin nanocrystals-loaded mannitol microparticles show promise as an inhalable treatment for respiratory diseases, combining effective aerodynamic properties with controlled drug release.

Identification of key necroptosis-related genes and immune landscape in patients with immunoglobulin A nephropathy

BackgroundImmunoglobulin A nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and kidney failure. Necroptosis is a novel type of programmed cell death that has been proved to be associated with the pathogenesis of infectious disease, cardiovascular disease, neurological disorders and so on. However, the role of necroptosis in IgAN remains unclear.MethodsIn this study, we explored the role of necroptosis-related genes in the pathogenesis of IgAN using a comprehensive bioinformatics method. Microarray datasets GSE93798 and GSE115857 were downloaded from Gene Expression Omnibus (GEO). “limma” package of R software was employed to identify necroptosis-related differentially expressed genes (NRDEGs) between IgAN and healthy controls. GO and KEGG functional enrichment analysis was performed by Clusterprofiler. Least absolute shrinkage and selection operator (LASSO) regression analysis identified hub NRDEGs. We further established a diagnostic model consisting of 7 diagnostic hub NRDEGs and validated the efficacy by an external dataset. The expression of hub genes was confirmed in sc-RNA dataset GSE171314. Immune infiltration, gene set enrichment analysis and transcription factor binding motifs enrichment analysis were conducted to further uncover their roles.Results1076 differentially expressed genes were identified between healthy individuals and IgAN patients from RNA-seq dataset GSE9379. Then we cross-linked them with necroptosis-related genes to obtain 9 NRDEGs. LASSO regression analysis screened out 7 hub genes (JUN, CD274, SERTAD1, NFKBIA, H19, UCHL1 and EZH2) of IgAN. We further conducted functional enrichment analysis and constructed the diagnostic model based on dataset GSE93798. GSE115857 was used as the independent validation cohort and indicated a great predictive efficacy. Immune infiltration, gene set enrichment analysis and transcription factor binding motifs enrichment analysis revealed their potential function. Finally, we screened out four drugs that were predicted to have therapeutic value of IgAN.ConclusionsIn summary, we identified 7 hub necroptosis-associated genes, which can be used as potential genetic biomarkers for IgAN prediction and treatment. Four drugs were predicted as the potential therapeutic solutions. Collectively, we provided insights into the necroptosis-related mechanisms and treatment of IgAN at the transcriptome level.

The Use of Diatomite-Based Composites for the Immobilization of Toxic Heavy Metals in Industrial Wastes Using Post-Flotation Sediment as an Example

Composite materials based on diatomite (DT) with the addition of biochar (BC), dolomite (DL), and bentonite (BN) were developed. The effect of chemical modification on the chemical structure of the resulting composites was investigated, and their influence on heavy metal immobilization and the ecotoxicity of post-flotation sediments was evaluated. It was demonstrated that the chemical modifications resulted in notable alterations to the chemical properties of the composites compared to pure DT and mixtures of DT with BC, DL, and BN. An increase in negative charge was observed in all variants. The addition of BC introduced valuable chemically and thermally resistant organic components into the composite. Among the chemical modifications, composites with the addition of perlite exhibited the lowest values of negative surface charge, which was attributed to the dissolution and transformation of silicon compounds and traces of kaolinite during their initial etching with sodium hydroxide. The materials exhibited varying efficiencies in metal immobilization, which is determined by both the type of DT additive and the type of chemical modification applied. The greatest efficacy in reducing the mobility of heavy metals was observed in the PFS with the addition of DT and BC without modification and with the addition of DT and BC after the modification of H2SO4 and H2O2: Cd 8% and 6%; Cr 71% and 69%; Cu 12% and 14%; Ni 10% and Zn 15%; and 4% and 5%. In addition, for Zn and Pb, good efficacy in reducing the content of mobile forms of these elements was observed for DT and DL without appropriate modification: 4% and 20%. The highest reduction in ecotoxicity was observed in the PFS with the addition of DT and BC, followed by BN and DL, which demonstrated comparable efficacy to materials with DT and BN.

Pharmacotherapy of systemic lupus erythematosus: A comparison of lupus disease activity with rituximab and sifalimumab

Systemic Lupus Erythematosus is a disease that affects millions worldwide. Research indicates that people suffering from lupus respond well to monoclonal antibody treatment aimed at characteristic immune cell markers. By targeting immune cell markers, the immune system is subsequently suppressed in a way such that lupus disease activity is decreased. Monoclonal antibody treatments targeted towards a variety of immune cell markers have historically been shown to result in decreases in lupus disease activity. Many studies have assessed lupus disease activity with monoclonal antibody treatments, but few have compared different treatments. A systematic review of a study that assessed the lupus disease activity for those taking rituximab was then compared to the findings of another study which assessed the lupus disease activity with those taking sifalimumab. The patients treated with sifalimumab had significantly decreased lupus disease activity when compared with other matched controls. Those who were treated with rituximab had significantly decreased lupus disease activity when compared with other matched controls. However, those who were treated with rituximab had a greater reduction of lupus disease activity as compared to control groups than did those who were treated with sifalimumab. Monoclonal antibody treatments for systemic lupus erythematosus are widespread. It is critical that these treatments are compared in order to find those with the greatest efficacy. For this review, rituximab seemed to have a greater reduction of disease activity than did sifalimumab. Further studies with greater sample sizes assessing multiple other side effects of monoclonal antibody immunosuppression are needed.

Leading edge biosensing applications based on AIE technology

Luminescent materials provide a unique method for biological imaging. Luminescent probes can label molecules of interest and present luminescent signals. Bioluminescence bioimaging has shown great efficacy in environmental, live cell and animal studies. Light-emitting materials play a very wide role in the field of light-emitting devices and biosensing. Luminescent materials are usually used as solid films or aggregate states. However, it is difficult to monitor the selectivity and sensitivity of various ions and small molecules in living cells with ordinary luminescent materials due to the changes in various aspects of analytes. Organic luminescent materials exhibit aggregation-induced quenching (ACQ) on molecular aggregation, and the ACQ effect is very common, which greatly limits the application of luminescent materials in chemical sensing, especially in biological imaging. Academician Tang Benzhong proposed “aggregation-induced emission (AIE)" as a powerful method to solve the ACQ problem for the first time. In this paper, the working principle of AIE is reviewed, and the research on the core working mechanism of AIE technology is not only of great fundamental significance, but also can pave the way for practical innovation of AIE technology applications. In this review, we outline the current basic understanding of the working mechanism of AIE, collate the cutting-edge biosensing applications based on AIE technology, including applications based on AIE in substance detection, biological detection, and disease detection. At last, we discuss the future development of AIE research.

Development of HPLC-UV method for determination of Nilotinib in spiked human plasma with greenness assessment

One of the approved second-generation tyrosine kinase inhibitors (Nilotinib) shows great efficacy and selectivity in the treatment of patients with chronic or accelerated phase chronic myelogenous leukemia, and in resistant/ intolerant to prior therapy cases. For the analysis of Nilotinib in synthetic mixture and human plasma samples, a new reversed-phase high-performance liquid chromatographic method was developed. Determination was performed successfully using RP–18 column and a mobile phase consisting of 10 mM potassium dihydrogen phosphate buffer (pH = 5.5), methanol, and acetonitrile in the ratio 37:37:26 (v/v/v). Isocratic mode of elution with flow rate 1.2 ml/min and UV detection at 265 nm were applied. The method was validated for linearity in the range 0.5–24.0 µg/ml and best accuracy and precision results were obtained at temperature 40 °C. The percentage recovery of the analyzed drug was in the range 88.0–106.0 %. Moreover, the proposed RP-HPLC method was evaluated in terms of greenness, whiteness and blueness using three newly developed ecological metrics – The Analytical Greenness software, White Analytical Chemistry and Blue Applicability Grade Index. Good results were obtained and the technique was proved effective, specific and suitable for implementation in routine quality control and clinical laboratory practice for therapeutic drug monitoring.

The behavior change effect of Levetriacetam in absence seizure

Abstract. The absence seizure is characterized by loss of consciousness and appears as a 3-5 Hz spike wave like discharge in electroencephalography (EEG) recording. Levetiracetam mainly works on the SV2A molecule, which can mediate neurotransmitter release. Compared with other antipsychotics, levetriacetam has shown great tolerance, fewer side effects and great efficacy. However, levetriacetam may alter the patients cognition and behavior in two different directions, enhance the cognition or become more aggressive. This change does not relate to the dose intake or other factors, it may be associated with the personal trait dopaminergic related gene. One possible explanation for this is that the dopaminergic related gene that can impact a persons trait can determine the adverse effect of levetriacetam. Understanding the relationship between the levetiracetam (LEV), absence seizure and behavior change can improve the safety of LEV modification, in this paper, there is the discussion about the role of the dopamine in the absence seizure, LEV pharmocology and behavior change.

Abstract A005: Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors

Abstract Background: Vascular endothelial-derived growth factor A(VEGFA) has been proven to be integral in the molecular pathogenesis of metastasis and tumor growth. It is known that VEGF is responsible for encoding a heparin-binding protein, which exists as a disulfide-linked homodimer which serves to promote the propagation and movement of vascular endothelial cells. This is essential for both pathological and physiological angiogenesis. CETC and cancer stem cells are potent secretors of VEGFA which is an essential cytokine that facilitates new vascular vessel formation, thus further enabling metastatic tumor growth. Methods: We developed a new extracorporeal microbind affinity blood filter platform technology with active heparane sulfate receptors (onco seraph). Heparin is cleaved into short chains which are permanently covalently bound to ultrahigh molecular weight polyethylene (UHMWPE) surfaces to create a new composition of matter. Liquid biopsy established high capacity for the rapid removal of CETC and PDAC cancer stem cells. Onco seraph was investigated in a dose escalation phase I/II clinical trial in adult patients with advanced and relapsed/refractory solid (what) and/or PDAC after standard of care and other lines of therapy failed in preventing disease progression. Results: To date 12 patients have been treated with onco seraph. No patient experienced treatment related adverse effects. Best responses include complete responses and stable disease at a low oncoseraph dose. Greatest efficacy was observed for patients whose liquid biopsy revealed significant and rapid reduction of CETC and cancer stem cells, followed by greater than 50% reduction in circulating VEGFA. Conclusions: This data supports the conclusion that the onco seraph platform technology is safe and has a high therapeutic value as an extracorporeal treatment for metastatic solid tumors refractory to standard of care. Citation Format: Sanja ILIC, Vedran Premuzic, Robert Ward. Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A005.

Ameliorative Effects of Essential Oils on Diabetes Mellitus: A Review.

Diabetes mellitus (DM) is a metabolic disorder and is responsible for the death of more than 4.2 million people in 2019. Synthetic drugs for DM like metformin have been reported to induce numerous complications and side effects. Reports suggested that essential plant oil has been used as an herbal remedy to lower blood glucose levels. Essential oils (EOs) are complex combinations of small molecules obtained from plants via the process of steam distillation and several solvents. EOs have already shown great efficacy as antimicrobials, anti-inflammatory, hepatoprotective, and anti-hypertensive. This review aims to summarize some potential EOs that have been reported to have anti-diabetic activity both in preclinical and clinical aspects while summarizing the probable mechanism of action. The authors went through a vast number of articles from various scientific databases like Google Scholar, PubMed, and Web of Science. It was found that EO from a total of 20 plants has been pre-clinically investigated to have anti-diabetic potential. Besides this, clinical studies have reported the antidiabetic efficacy of EOs from Nigella sativa and Cuminum cyminum at different concentrations. Bioactive phytoconstituents like carvacrol, thymol, α- pinene, via . obtained from EOs ameliorate DM by inhibiting α-GLUC, α-amylase, lipase enzymes and increasing GLUT-4 expression, AKT phosphorylation, via . Although fewer in number, EOs from plant sources have demonstrated significant efficacy in DM. Proper elucidation of the anti-diabetic efficacy of the EOs may open up new avenues for drug discovery and development subjected to clinical studies.

A Systematic Review and Meta-analysis of Efficacy and Safety of Mavacamten for the Treatment of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common hereditary cardiomyopathy. Mavacamten, a first-in-class cardiac myosin inhibitor, is considered to be a specific drug for the treatment of HCM. This meta-analysis aimed to assess the efficacy and safety of mavacamten in patients with HCM. PubMed, Cochrane Library, Embase and Clinical Trials.gov databases were searched from inception to February 6, 2024 for randomized controlled trials (RCTs) which compared the efficacy and safety between mavacamten and placebo in treating HCM. Six RCTs involving 732 patients were included in this meta-analysis. This meta-analysis showed that mavacamten improved the New York Heart Association (NYHA) function class [risk ratios (RR): 2.21, 95% confidence interval (CI): 1.48 to 3.30, p = 0.00001], Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS) scores [mean difference (MD): 9.33, 95% CI: 7.09 to 11.57, p < 0.00001] and composite functional end point (RR: 1.86, 95% CI: 1.25 to 2.78, p = 0.002). Meanwhile, mavacamten decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: -492.28, 95% CI: -611.55 to -373.02, p < 0.00001), cardiac troponin I (cTnI) (MD: -14.58, 95% CI: -26.98 to -2.17, p = 0.02) and Valsalva left ventricular outflow tract (LVOT) gradient (MD: -57.96, 95% CI: -82.15 to -33.78, p < 0.00001). The results for the incidence of ≥1 total emergent adverse event (TEAE) and ≥1 serious adverse event (SAE) showed that there was no significant difference between both groups (RR: 1.9, 95% CI: 0.97 to 1.24, p = 0.16) (RR: 1.06, 95% CI: 0.46 to 2.44, p = 0.90). Mavacamten has great efficacy for the treatment of HCM. Meanwhile, mavacamten did not increase the incidence of adverse events or serious adverse events.

Assessment the Efficacy of the CRISPR System for Inducing Mutations in the AIMP2 Gene to Create a Cell Line Model of HLD17 Disease.

Hypomyelinating leukodystrophy-17 is a neurodevelopmental disorder caused by autosomal recessive mutations in the AIMP2 gene, resulting in a lack of myelin deposition during brain development, leading to variable neurological symptoms. Research on brain function in these disorders is challenging due to the lack of access to brain tissue. To overcome this problem, researchers have utilized different cell and animal models. The CRISPR-Cas9 system is considered the most optimal and effective method for genetic modification and developing cell models. We studied the efficacy of the CRISPR-Cas9 technology in inducing mutations in the AIMP2 gene in HEK293 cell lines. The study involved transfecting HEK293 cells with recombinant PX458 plasmids targeting spCas-9 and AIMP2 sgRNA. The cells were evaluated using fluorescent microscopy and enriched using serial dilution. The CRISPR/Cas9 plasmids were validated through PCR and Sanger sequencing. After serial dilution, AS-PCR, Sanger sequencing, and TIDE program analysis showed the construct successfully induces an indel mutation in HEK cells. Our findings demonstrated the great efficacy of the CRISPR system and produced a construct for inducing mutations in the AIMP2 gene, which can be utilized to edit the AIMP2 gene in nerve cells and create a cellular model of the HLD17 disease.

Application of preoperative advanced diffusion magnetic resonance imaging in evaluating the postoperative recurrence of lower grade gliomas

BackgroundRecurrence of lower grade glioma (LrGG) appeared to be unavoidable despite considerable research performed in last decades. Thus, we evaluated the postoperative recurrence within two years after the surgery in patients with LrGG by preoperative advanced diffusion magnetic resonance imaging (dMRI).Materials and methods48 patients with lower-grade gliomas (23 recurrence, 25 nonrecurrence) were recruited into this study. Different models of dMRI were reconstructed, including apparent fiber density (AFD), white matter tract integrity (WMTI), diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), Bingham NODDI and standard model imaging (SMI). Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) was used to construct a multiparametric prediction model for the diagnosis of postoperative recurrence.ResultsThe parameters derived from each dMRI model, including AFD, axon water fraction (AWF), mean diffusivity (MD), mean kurtosis (MK), fractional anisotropy (FA), intracellular volume fraction (ICVF), extra-axonal perpendicular diffusivity (De⊥), extra-axonal parallel diffusivity (De∥) and free water fraction (fw), showed significant differences between nonrecurrence group and recurrence group. The extra-axonal perpendicular diffusivity (De⊥) had the highest area under curve (AUC = 0.885), which was significantly higher than others. The variable importance for the projection (VIP) value of De⊥ was also the highest. The AUC value of the multiparametric prediction model merging AFD, WMTI, DTI, DKI, NODDI, Bingham NODDI and SMI was up to 0.96.ConclusionPreoperative advanced dMRI showed great efficacy in evaluating postoperative recurrence of LrGG and De⊥ of SMI might be a valuable marker.

The First Triple Agonist for Antiobesity: Retatrutide

The prevalence of individuals with overweight and obesity has increased by 18% since 1990 and it is projected that by 2030, nearly 50% of US adults will have obesity. Lifestyle modifications, such as diet and exercise, typically lead to approximately 3–5% weight loss, whereas 5–15% weight loss is necessary to significantly impact obesity-associated comorbidities and improve overall health outcomes. In addition to lifestyle modifications, pharmacotherapy has been utilized as an adjunctive treatment to increase weight loss and improve health outcomes. The Food and Drug Administration has currently approved 6 drugs to treat overweight and obesity, with the recently approved drugs surging in popularity after demonstrating superior weight loss outcomes. Additionally, a number of agents are in the pipeline, offering promise of unprecedented degrees of weight loss. One such drug is retatrutide, which is a triple agonist targeting the glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor, and glucagon receptor. Phase 1 and 2 clinical trials have demonstrated the safety, tolerability, and pharmacokinetics of retatrutide in patients with obesity and/or type 2 diabetes. The pharmacokinetics of retatrutide were dose proportional and its mean half-life of approximately 6 days supported a once-weekly dosing. The safety profile was similar to GLP-1R agonists and glucose-dependent insulinotropic polypeptide receptor/GLP-1R co-agonists, with gastrointestinal disorders being the most common adverse effects reported. Each trial demonstrated greater weight loss with retatrutide treatment in comparison to placebo, with greatest efficacy at higher doses. Overall, these clinical trials have demonstrated the superior efficacy of retatrutide as a weight loss medication in patients with overweight and obesity.

Wipe Disinfection of Reusable Elastomeric Half-Mask Respirators for Health Care Use.

During shortages, elastomeric half-mask respirators (EHMRs) are an alternative to reusing N95 filtering facepiece respirators but require between-use disinfection. The objectives of this study were to (a) measure microbial reductions on EHMR surfaces under laboratory conditions by a standardized procedure using wipes impregnated with health care disinfectants and to (b) measure microbial reductions on EHMRs disinfected by volunteer health care providers. We inoculated EHMR (Honeywell model RU8500) surfaces with Pseudomonas aeruginosa, Bacillus atrophaeus spores, and bacteriophages MS2 and Φ6, and disinfected them using two wipes with hydrogen peroxide (HP), alcohols, and quaternary ammonium compounds (QACs). Then, we randomized 54 volunteer subjects into three groups (Group 1: two wipes with instructions, Group 2: five wipes with instructions, Group 3: no instructions or set number of wipes) and used 0.5% HP wipes without precleaning on EHMRs inoculated with Raoultella terrigena and MS2. The laboratory study demonstrated that all organisms achieved at least 4 log10 median reductions (HP>QAC/alcohol>QAC>QAC/saline). Pseudomonas was highly susceptible to HP and QAC/alcohol and Φ6 to all disinfectants. MS2 reduction was highest using HP and lowest using QAC/saline. Bacillus was least susceptible. The volunteer study showed a 3 to 4 log10 average reductions of bacteria and virus; Raoultella reductions were greater than MS2, with variability within and between subjects. Conclusions: HP disinfectant wipes used in laboratory and by volunteers reduce bacteria and viruses on EHMRs by 3 to 4 log10 on average. Commercially available hospital disinfectant wipes reduce bacteria and viruses on EHMRs and can fill the need for between-use disinfection. HP and combination QAC/alcohol have the greatest efficacy under our test conditions.

Efficacy and safety of treat-and-extend intravitreal brolucizumab in naive and switched patients with macular neovascularization: one-year follow-up study

Backgroundto analyze, at one year, the efficacy and safety of treat-and-extend (T&E) intravitreal (IV) Brolucizumab in patients affected by macular neovascularization (MNV). Both naïve and previously treated (i.e., switched) patients were included, and the data from the two groups were compared.Methodsanatomical (i.e., central subfoveal thickness, CST; presence of fluid), functional (i.e., best corrected visual acuity, BCVA) and treatment-related (i.e., number of IV injections within the study period; number of patients reaching a 12-weeks interval between treatments) data from 41 eyes of 41 subjects (20 naïve and 21 switched) were analyzed. Patients were treated with 3 monthly IV injections followed by a T&E regimen based on a disease activity assessment performed at each scheduled IV treatment.Resultssignificant CST reduction (from 412.1 ± 115.8 to 273.2 ± 61.6; p < 0.05) and BCVA (mean; p) improvement were observed in the naïve group, while in the switched cohort, both parameters were almost stable. In the naïve and switched groups, 55% and 33.5% of patients, respectively, reached a 12-week IV interval at one year, with a mean of 6.55 ± 1 and 7.43 ± 0.68 IV treatments, respectively. One patient with mild anterior uveitis without sequelae was recorded.ConclusionIn patients with MNV, IV Brolucizumab injections following a T&E regimen demonstrated great efficacy and a good safety profile, with greater anatomical and functional results in naïve patients.Trial registrationThis study was approved by the Local Ethics Committee (protocol number 155/2020, general registry number n°11486, InterHospital Ethics Committee, San Luigi Gonzaga Hospital, Orbassano, Italy).

Efficacy of Certain Bio-Pesticides against the Major Insect Pests of Broccoli (Brassica oleracea var. italica L.)

The field experiment was undertaken at the Experimental Farm, Department of Entomology, School of Agricultural Sciences (SAS), Medziphema Campus, Nagaland University, during the period of November 2021 to February 2022 to study the efficacy of certain bio-pesticides against major insect pests of broccoli. The experiment was conducted using Randomized Block Design (RBD) with six treatments including control and replicated four times. The study revealed that Indian cabbage white, Pieris spp. and green peach aphid, Myzus persicae have been found to be the major insect pest in broccoli. It is recorded that the highest (73.49%) population reduction of M. persicae was obtained from the plot treated with emamectin benzoate 5% SG and the highest (90.16%) population reduction of Pieris spp. was recorded on the plot treated with spinosad 45% SG. Therefore, the study concluded that use of bio-pesticides offers a great efficacy in controlling the pest and diminish the pesticides related issue.

Efficacy of Levetiracetam vs Phenobarbital as First Line Therapy for the Treatment of Neonatal Seizures

OBJECTIVE Seizures are one of the most common neurologic complications seen in a neonate. Historically, phenobarbital has been the agent of choice, but can lead to adverse neurologic outcomes, which has contributed to the use of other agents. Levetiracetam has proven great efficacy with an excellent safety profile in older patients, causing interest of its use in neonates. The objective of this study was to determine if levetiracetam would provide similar neonatal seizure resolution rates as phenobarbital. METHODS The study was a single-center, retrospective, cohort study from August 1, 2020 to August 31, 2022 investigating the efficacy and safety of using levetiracetam compared with phenobarbital as a first line treatment for neonatal seizures. The primary outcome was to assess overall seizure resolution after administration of levetiracetam or phenobarbital, without addition of a second antiseizure medication. RESULTS There were 87 patients included in the study. Fifteen neonates (27.78%) achieved seizure resolution with phenobarbital compared with 9 neonates (27.27%) who received levetiracetam first line (p = 0.959). Neonates who received phenobarbital had higher rates of adverse effects. Neonates who received a benzodiazepine prior to administration of levetiracetam had lower seizure resolution rates (p = 0.021). CONCLUSIONS These findings suggest there is no difference in using phenobarbital over levetiracetam to achieve complete seizure resolution in a neonate. Higher rates of adverse events were seen in the phenobarbital group. The use of a benzodiazepine prior to administration of levetiracetam may reduce the efficacy of levetiracetam.

Pharmacognosic Study and Determination of Marker Compounds Soursop Leaves (Annona muricata)

Soursop (Annona muricata) is reported to have great efficacy in traditional medicine in Indonesia so it is very vulnerable to being faked or sold as low quality. Apart from having a delicious fruit taste, Soursop leaves have also been used as an effective cancer medicine by the public and have been scientifically proven so that Soursop can be used as a phytopharmaceutical product. Therefore, it is necessary to carry out research to determine pharmacognosy parameters and marker compounds as ingredients needed to obtain the authenticity of simplicia and plant extracts. This research includes macroscopic and microscopic examination of leaves, macroscopic and microscopic examination of simplicia, fluorescence characteristics of simplicia, determining the solubility of methanol extract in various non-polar and polar solvents as well as the characteristics of marker compounds that can be used as alternatives to existing marker compounds from Soursop (Annona muricata). The research results obtained are important information as a stage for the identification and standardization of soursop leaves (Annona muricata) as a raw material for herbal medicine.

Urine-derived stem cells serve as a robust platform for generating native or engineered extracellular vesicles

BackgroundMesenchymal stromal cell (MSC) therapy holds great potential yet efficacy and safety concerns with cell therapy persist. The beneficial effects of MSCs are often attributed to their secretome that includes extracellular vesicles (EVs). EVs carry biologically active molecules, protected by a lipid bilayer. However, several barriers hinder large-scale MSC EV production. A serum-free culturing approach is preferred for producing clinical-grade MSC-derived EVs but this can affect both yield and purity. Consequently, new strategies have been explored, including genetically engineering MSCs to alter EV compositions to enhance potency, increase circulation time or mediate targeting. However, efficient transfection of MSCs is challenging. Typical sources of MSC include adipose tissue and bone marrow, which both require invasive extraction procedures. Here, we investigate the use of urine-derived stem cells (USCs) as a non-invasive and inexhaustible source of MSCs for EV production.MethodsWe isolated, expanded, and characterized urine-derived stem cells (USCs) harvested from eight healthy donors at three different time points during the day. We evaluated the number of clones per urination, proliferation capacity and conducted flow cytometry to establish expression of surface markers. EVs were produced in chemically defined media and characterized. PEI/DNA transfection was used to genetically engineer USCs using transposon technology.ResultsThere were no differences between time points for clone number, doubling time or viability. USCs showed immunophenotypic characteristics of MSCs, such as expression of CD73, CD90 and CD105, with no difference at the assessed time points, however, male donors had reduced CD73 + cells. Expanded USCs were incubated without growth factors or serum for 72 h without a loss in viability and EVs were isolated. USCs were transfected with high efficiency and after 10 days of selection, pure engineered cell cultures were established.ConclusionsIsolation and expansion of MSCs from urine is non-invasive, robust, and without apparent sex-related differences. The sampling time point did not affect any measured markers or USC isolation potential. USCs offer an attractive production platform for EVs, both native and engineered.

Correlation analysis of cofilin-1 with renal prognosis in primary IgA nephropathy

PurposeThe purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN).MethodsPatients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis.Results133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803).ConclusionCofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN.