Safety evaluation of Plukenetia volubilis seeds: a metabolomic profiling and network toxicology approach.

Sacha Inchi (Plukenetia volubilis) seeds and oil have been integrated into daily diets. However, scientific reports have raised concerns regarding potential health risks associated with saponins and alkaloids in this seeds. This study employed a combination analysis using proton-NMR, GC-MS, LC-QTOF, and GNPS molecular networking to evaluate the chemical composition of these seeds. In silico toxicology analysis and in vitro cytotoxicity assays were conducted to investigate the potential toxicity effects of Sacha Inchi seeds and their contained metabolites. The results revealed that major components of these seeds are oils (linoleic, linolenic, and oleic acids) and sugars, with minor amounts of phytosterols and trigonelline, a pyridine alkaloid. GNPS analysis suggested the absence of saponins, instead, it identified trigonelline and a few other nitrogen-containing metabolites (amino acids and oligopeptides). In silico toxicology analysis indicated that this sample did not exhibit toxicity. Furthermore, in vitro cytotoxicity screening demonstrated no cytotoxic effects against NIH-3T3 cells, even at 400 µg mL-1. In general, these findings collectively indicated the absence of saponins, the presence of phytosterols and trigonellin (a pyridine alkaloid), and a low safety risk related to saponin and alkaloid content in the Sacha Inchi seeds.

Platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as predictors of refractory anaphylaxis.

Background: Refractory anaphylaxis poses an ongoing, lethal hypersensitivity response that unpredictably involves multiple organs despite appropriate intramuscular (IM) adrenaline injections. Studies on the association of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) concerning anaphylactic severity have yet to be carried out. The study aimed to evaluate the association between blood PLR and NLR levels and refractory anaphylaxis. Methods: We carried out a retrospective cross-sectional study in which medical records of patients with anaphylaxis who sought urgent care at the Emergency Department (ED) of Tertiary Hospital in Hanoi, Vietnam, were evaluated. Based on the United Kingdom Resuscitation Council guidelines in 2021, patients were classified as refractory anaphylaxis if they needed more than two appropriate doses of intramuscular adrenaline for anaphylactic symptoms resolution. Clinical data and laboratory results were obtained in the medical records. Logistic regression analysis determined the association between contributing factors and refractory anaphylaxis. Results: One-hundred eighteen adults (age 51.80 ± 18.25 years) were analyzed, including 38 refractory anaphylaxis patients (32.2%). Refractory anaphylaxis patients exhibited notably elevated platelet-to-lymphocyte ratio (PLR) (P = 0.006) and increased neutrophil-to-lymphocyte ratio (NLR) (P < 0.001) in comparison to non-refractory anaphylaxis patients. Receiver operating characteristic curve (ROC) analysis demonstrated an optimal PLR cutoff value of 129.5 (area under the ROC curve [AUC] 0.658, sensitivity 73.68%, specificity 61.25%, P = 0.004) and an optimal NLR cutoff value of 4 (AUC 0.736, sensitivity 65.79%, specificity 73.75%, P < 0.001) for refractory anaphylaxis. Multivariate logistic regression analysis revealed a PLR≥129.5 (OR = 4.83, 95% CI: 1.87-12.48) and an NLR≥4 (OR = 4.60, 95% CI: 1.86-11.41) were independently associated with refractory anaphylaxis. Conclusion: Elevated PLR and NLR serve as independent indicators significantly associated with refractory anaphylaxis.

Rhinoplasty Exclusively Utilizing Autologous Costal Cartilage for Patients with Prior Unilateral Cleft Lip Repair.

Background: Rhinoplasty in patients with previous unilateral cleft lip repair is a surgical challenge due to complex nasal deformities, including a horizontally positioned nasal wing, wide cleft side nostrils, nasal base defects, and a short and deviated nasal columella. To comprehensively address these complexities, we exclusively utilized autologous costal cartilage in rhinoplasty procedures, using various surgical techniques. Methods: This study presents a comprehensive case series of 39 patients who had previously undergone unilateral cleft lip surgery but still had nasal deformities. Rhinoplasty using autologous costal cartilage was performed at Cho Ray Hospital, Vietnam. Costal cartilage was partially crushed and then finely cut to shape the dorsal area and raise the nasal base on the cleft side. Partially crushed cartilage was also used to shape shield grafts, cap grafts, and alar batten grafts, whereas sliced cartilage was utilized for septal extension grafts. Evaluation was based on improvements in anthropometric indicators, patient satisfaction using Rhinoplasty Outcome Evaluation (ROE) scale and FACE-Q scores. Results: The average age of patients was 25.13 years. All postoperative anthropometric indicators showed significant improvements. Postsurgery, the total ROE score was three times higher than before surgery (P < 0.001), and the total FACE-Q score was 2.26 times higher (P < 0.001). No significant intraoperative or postoperative complications were observed. Conclusions: This procedure effectively addresses complex nasal deformities in patients with prior unilateral cleft lip repair, emphasizing the value of autologous costal cartilage in rhinoplasty for such individuals.

Promotion of Th17 Polarized Immunity via Co-Delivery of Mincle Agonist and Tuberculosis Antigen Using Silica Nanoparticles.

Adjuvants and immunomodulators that effectively drive a Th17-skewed immune response are not part of the standard vaccine toolkit. Vaccine adjuvants and delivery technologies that can induce Th17 or Th1/17 immunity and protection against bacterial pathogens, such as tuberculosis (TB), are urgently needed. Th17-polarized immune response can be induced using agonists that bind and activate C-type lectin receptors (CLRs) such as macrophage inducible C-type lectin (Mincle). A simple but effective strategy was developed for codelivering Mincle agonists with the recombinant Mycobacterium tuberculosis fusion antigen, M72, using tunable silica nanoparticles (SNP). Anionic bare SNP, hydrophobic phenyl-functionalized SNP (P-SNP), and cationic amine-functionalized SNP (A-SNP) of different sizes were coated with three synthetic Mincle agonists, UM-1024, UM-1052, and UM-1098, and evaluated for adjuvant activity in vitro and in vivo. The antigen and adjuvant were coadsorbed onto SNP via electrostatic and hydrophobic interactions, facilitating multivalent display and delivery to antigen presenting cells. The cationic A-SNP showed the highest coloading efficiency for the antigen and adjuvant. In addition, the UM-1098-adsorbed A-SNP formulation demonstrated slow-release kinetics in vitro, excellent stability over 12 months of storage, and strong IL-6 induction from human peripheral blood mononuclear cells. Co-adsorption of UM-1098 and M72 on A-SNP significantly improved antigen-specific humoral and Th17-polarized immune responses in vivo in BALB/c mice relative to the controls. Taken together, A-SNP is a promising platform for codelivery and proper presentation of adjuvants and antigens and provides the basis for their further development as a vaccine delivery platform for immunization against TB or other diseases for which Th17 immunity contributes to protection.

Influence of purple non-sulfur bacterial augmentation on soil nutrient dynamics and rice (Oryza sativa) growth in acidic saline-stressed environments.

The aim of the current study was to assess the potency of the exopolymeric substances (EPS)-secreting purple non-sulfur bacteria (PNSB) on rice plants on acidic salt-affected soil under greenhouse conditions. A two-factor experiment was conducted following a completely randomized block design. The first factor was the salinity of the irrigation, and the other factor was the application of the EPS producing PNSB (Luteovulum sphaeroides EPS18, EPS37, and EPS54), with four replicates. The result illustrated that irrigation of salt water at 3-4‰ resulted in an increase in the Na+ accumulation in soil, resulting in a lower rice grain yield by 12.9-22.2% in comparison with the 0‰ salinity case. Supplying the mixture of L. sphaeroides EPS18, EPS37, and EPS54 increased pH by 0.13, NH4+ by 2.30 mg NH4+ kg-1, and available P by 8.80 mg P kg-1, and decreased Na+ by 0.348 meq Na+ 100 g-1, resulting in improvements in N, P, and K uptake and reductions in Na uptake, in comparison with the treatment without bacteria. Thus, the treatments supplied with the mixture of L. sphaeroides EPS18, EPS37, and EPS54 resulted in greater yield by 27.7% than the control treatment.

De novo copy number variations in candidate genomic regions in patients of severe autism spectrum disorder in Vietnam.

Autism spectrum disorder (ASD) is a developmental disorder with a prevalence of around 1% children worldwide and characterized by patient behaviour (communication, social interaction, and personal development). Data on the efficacy of diagnostic tests using copy number variations (CNVs) in candidate genes in ASD is currently around 10% but it is overrepresented by patients of Caucasian background. We report here that the diagnostic success of de novo candidate CNVs in Vietnamese ASD patients is around 6%. We recruited one hundred trios (both parents and a child) where the child was clinically diagnosed with ASD while the parents were not affected. We performed genetic screening to exclude RETT syndrome and Fragile X syndrome and performed genome-wide DNA microarray (aCGH) on all probands and their parents to analyse for de novo CNVs. We detected 1708 non-redundant CNVs in 100 patients and 118 (7%) of them were de novo. Using the filter for known CNVs from the Simons Foundation Autism Research Initiative (SFARI) database, we identified six CNVs (one gain and five loss CNVs) in six patients (3 males and 3 females). Notably, 3 of our patients had a deletion involving the SHANK3 gene-which is the highest compared to previous reports. This is the first report of candidate CNVs in ASD patients from Vietnam and provides the framework for building a CNV based test as the first tier screening for clinical management.

Effects of excipients on the interactions of self-emulsifying drug delivery systems with human blood plasma and plasma membranes.

Due to its versatility in formulation and manufacturing, self-emulsifying drug delivery systems (SEDDS) can be used to design parenteral formulations. Therefore, it is necessary to understand the effects of excipients on the behavior of SEDDS formulations upon parenteral administration, particularly their interactions with blood plasma and cell membranes. In this study, we prepared three neutrally charged SEDDS formulations composed of medium-chain triglycerides as the oil phase, polyoxyl-35 castor oil (EL35) and polyethylene glycol (15)-hydroxystearate (HS15) as the nonionic surfactants, medium-chain mono- and diglycerides as the co-surfactant, and propylene glycol as the co-solvent. The cationic surfactant, didodecyldimethylammonium bromide (DDA), and the anionic surfactant, sodium deoxycholate (DEO), were added to the neutral SEDDS preconcentrates to obtain cationic and anionic SEDDS, respectively. SEDDS were incubated with human blood plasma and recovered by size exclusion chromatography. Data showed that SEDDS emulsion droplets can bind plasma protein to different extents depending on their surface charge and surfactant used. At pH 7.4, the least protein binding was observed with anionic SEDDS. Positive charges increased protein binding. SEDDS stabilized by HS15 can adsorb more plasma protein and induce more plasma membrane disruption activity than SEDDS stabilized by EL35. These effects were more pronounced with the HS15 + DDA combination. The addition of DDA and DEO to SEDDS increased plasma membrane disruption (PMD) activities, and DDA (1% w/w) was more active than DEO (2% w/w). PMD activities of SEDDS were concentration-dependent and vanished at appropriate dilution ratios.

Speculum-free portable preterm imaging system.

Significance: Preterm birth is defined as a birth before 37 weeks of gestation and is one of the leading contributors to infant mortality rates globally. Premature birth can lead to life-long developmental impairment for the child. Unfortunately, there is a significant lack of tools to diagnose preterm birth risk, which limits patient care and the development of new therapies. Aim: To develop a speculum-free, portable preterm imaging system (PPRIM) for cervical imaging; testing of the PPRIM system to resolve polarization properties of birefringent samples; and testing of the PPRIM under an IRB on healthy, non-pregnant volunteers for visualization and polarization analysis of cervical images. Approach: The PPRIM can perform 4×3 Mueller-matrix imaging to characterize the remodeling of the uterine cervix during pregnancy. The PPRIM is built with a polarized imaging probe and a flexible insertable sheath made with a compatible flexible rubber-like material to maximize comfort and ease of use. Results: The PPRIM device is developed to meet specific design specifications as a speculum-free, portable, and comfortable imaging system with polarized imaging capabilities. This system comprises a main imaging component and a flexible silicone inserter. The inserter is designed to maximize comfort and usability for the patient. The PPRIM shows high-resolution imaging capabilities at the 20 mm working distance and 25 mm circular field of view. The PPRIM demonstrates the ability to resolve birefringent sample orientation and full field capture of a healthy, non-pregnant cervix. Conclusion: The development of the PPRIM aims to improve access to the standard of care for women's reproductive health using polarized Mueller-matrix imaging of the cervix and reduce infant and maternal mortality rates and better quality of life.

Using Trichoderma asperellum to Antagonize Lasiodiplodia theobromae Causing Stem-End Rot Disease on Pomelo (Citrus maxima).

Stem-end rot disease has been causing damage to the production of pomelos in Vietnam. The cur-rent study aimed to (i) isolate fungal pathogens causing pomelo stem-end rot disease (PSERD) and (ii) discover Trichoderma spp. that had an antagonistic ability against pathogens under in vitro conditions. Fungi causing PSERD were isolated from pomelo fruits with symptoms of stem-end rot disease and collected from pomelo farms in Ben Tre province, Vietnam. Moreover, 50 fungal strains of Trichoderma spp. also originated from soils of these pomelo farms in Ben Tre province and were dual-tested with the fungal pathogen on the PDA medium. The results demonstrated that 11 pathogenic fungi causing PSERD were isolated from the fruit and showed mycelial growth of roughly 5.33-8.77 cm diameter at 72 h after inoculation. The two fungi that exhibited the fast-est growth, namely, S-P06 and S-P07, were selected. ITS sequencing of the S-P06 and S-P07 fungi resulted in Lasiodiplodia theobromae. All the 50 Trichoderma spp. strains were allowed to antago-nize against the S-P06 and S-P07 strains under in vitro conditions. The greatest antagonistic effi-ciency was found in Trichoderma spp. T-SP19 at 85.4-86.2% and T-SP32 at 84.7-85.4%. The two antagonists were identified as Trichoderma asperellum T-SP19 and T-SP32. The selected strains of Trichoderma asperellum were potent as a biological control for fruit plants.

Ensemble learning of myocardial displacements for myocardial infarction detection in echocardiography.

Background: Early detection and localization of myocardial infarction (MI) can reduce the severity of cardiac damage through timely treatment interventions. In recent years, deep learning techniques have shown promise for detecting MI in echocardiographic images. Existing attempts typically formulate this task as classification and rely on a single segmentation model to estimate myocardial segment displacements. However, there has been no examination of how segmentation accuracy affects MI classification performance or the potential benefits of using ensemble learning approaches. Our study investigates this relationship and introduces a robust method that combines features from multiple segmentation models to improve MI classification performance by leveraging ensemble learning. Materials and Methods: Our method combines myocardial segment displacement features from multiple segmentation models, which are then input into a typical classifier to estimate the risk of MI. We validated the proposed approach on two datasets: the public HMC-QU dataset (109 echocardiograms) for training and validation, and an E-Hospital dataset (60 echocardiograms) from a local clinical site in Vietnam for independent testing. Model performance was evaluated based on accuracy, sensitivity, and specificity. Results: The proposed approach demonstrated excellent performance in detecting MI. It achieved an F1 score of 0.942, corresponding to an accuracy of 91.4%, a sensitivity of 94.1%, and a specificity of 88.3%. The results showed that the proposed approach outperformed the state-of-the-art feature-based method, which had a precision of 85.2%, a specificity of 70.1%, a sensitivity of 85.9%, an accuracy of 85.5%, and an accuracy of 80.2% on the HMC-QU dataset. On the external validation set, the proposed model still performed well, with an F1 score of 0.8, an accuracy of 76.7%, a sensitivity of 77.8%, and a specificity of 75.0%. Conclusions: Our study demonstrated the ability to accurately predict MI in echocardiograms by combining information from several segmentation models. Further research is necessary to determine its potential use in clinical settings as a tool to assist cardiologists and technicians with objective assessments and reduce dependence on operator subjectivity. Our research codes are available on GitHub at https://github.com/vinuni-vishc/mi-detection-echo.

S-Protected Thiolated Chitosan versus Thiolated Chitosan as Cell Adhesive Biomaterials for Tissue Engineering.

Chitosan (Ch) and different Ch derivatives have been applied in tissue engineering (TE) because of their biocompatibility, favored mechanical properties, and cost-effectiveness. Most of them, however, lack cell adhesive properties that are crucial for TE. In this study, we aimed to design an S-protected thiolated Ch derivative exhibiting high cell adhesive properties serving as a scaffold for TE. 3-((2-Acetamido-3-methoxy-3-oxopropyl)dithio) propanoic acid was covalently attached to Ch via a carbodiimide-mediated reaction. Low-, medium-, and high-modified Chs (Ch-SS-1, Ch-SS-2, and Ch-SS-3) with 54, 107 and 140 µmol of ligand per gram of polymer, respectively, were tested. In parallel, three thiolated Chs, namely Ch-SH-1, Ch-SH-2, and Ch-SH-3, were prepared by conjugating N-acetyl cysteine to Ch at the same degree of modification to compare the effectiveness of disulfide versus thiol modification on cell adhesion. Ch-SS-1 showed better cell adhesion capability than Ch-SS-2 and Ch-SS-3. This can be explained by the more lipophilic surfaces of Ch-SS as a higher modification was made. Although Ch-SH-1, Ch-SH-2, and Ch-SH-3 were shown to be good substrates for cell adhesion, growth, and proliferation, Ch-SS polymers were superior to Ch-SH polymers in the formation of 3D cell cultures. Cryogels structured by Ch-SS-1 (SSg) resulted in homogeneous scaffolds with tunable pore size and mechanical properties by changing the mass ratio between Ch-SS-1 and heparin used as a cross-linker. SSg scaffolds possessing interconnected microporous structures showed good cell migration, adhesion, and proliferation. Therefore, Ch-SS can be used to construct tunable cryogel scaffolds that are suitable for 3D cell culture and TE.

Isolation and characterization of novel potassium-solubilizing purple nonsulfur bacteria from acidic paddy soils using culture-dependent and culture-independent techniques.

The current research as aimed (i) to isolate and select the purple nonsulfur bacteria (PNSB) possessing the potassium-solubilizing ability from acid paddy fields and (ii) to evaluate the ability to release the plant growth-promoting substances (PGPS) of selected PNSB. A total of 35 acid sulfate (AS) soil samples were collected in An Giang province, Vietnam. Then, 70 PNSB strains were isolated from the AS soil samples. In the current study, the isolated strains were screened and selected according to their tolerability to acidic conditions, ability to solubilize potassium, and characteristics of a plant growth promoter on basic isolation media with various incubation conditions. Therein, three strains, TT07.4, AN05.1, and AC04.1, presented the highest potassium solubilization under the microaerobic light (11.8-17.7 mg L-1) and aerobic dark (16.4-24.7 mg L-1) conditions and stresses from Al3+, Fe2+, and Mn2+ toxicity. The selected strains were identified as Rhodopseudomonas pentothenatexigens by the 16S rDNA sequence, with 99% similarity. The selected acidic-resistant strains possessed the traits of biofertilizers under both microaerobic light and aerobic dark conditions, with abilities to fix nitrogen (0.17-6.24; 7.93-11.2 mg L-1); solubilize phosphorus from insoluble compounds with 3.22-49.9 and 9.49-11.2 mg L-1 for Al-P, 21.9-25.8 and 20.2-25.1 mg L-1 for Ca-P, and 10.1-29.8 and 18.9-23.2 mg L-1 for Fe-P; produce 5-aminolevulinic acid (0.63-3.01; 1.19-6.39 mg L-1), exopolymeric substances (0.14-0.76; 0.21-0.86 mg L-1), indole-3-acetic acid (12.9-32.6; 13.6-17.8 mg L-1), and siderophores (28.4-30.3; 6.15-10.3%). The selected potassium-solubilizing strains have a great potential to apply in liquid form into rice seed and solid form in AS soils to supply nutrients and PGPS for enhancing rice growth and grain yield.

Improvement of Nutrient Uptake, Yield of Black Sesame (Sesamum indicum L.), and Alluvial Soil Fertility in Dyke by Spent Rice Straw from Mushroom Cultivation as Biofertilizer Containing Potent Strains of Rhodopseudomonas palustris.

The aim of the current research was to evaluate the effects of members of purple nonsulfur bacteria (PNSB), Rhodopseudomonas palustris strains of VNW02, TLS06, VNW64, and VNS89, mixed with spent rice straw (SRS) from mushroom cultivation as a carrier on promoting sesame growth and yield, and ameliorating the alluvial soil (AS) fertility in dykes. A 4 × 3 factorial experiment consisting of different levels of the solid PNSB biofertilizer mixture at 0, 3, 4, and 5 t·ha-1 (0, 1.81 × 108, 2.24 × 108, and 2.68 × 108 cells pot-1, respectively), and nitrogen (N) and phosphorus (P) inorganic fertilizer rates (100, 75, and 50 kg·N·ha-1; 60, 45, and 30 kg P2O5·ha-1, respectively) was performed in pots with the sesame variety of ADB1 in the dyked AS. The solid PNSB biofertilizer mixture at at least 3 t·ha-1 significantly enhanced the sesame seed yield by providing higher macronutrients for plants by increasing available N and soluble P concentrations in the soil. The solid PNSB biofertilizer mixture in addition to 75% of the recommended N and P fertilizers produced an equivalent yield in comparison to the utilized 100% of N and P inorganic fertilizers. The solid PNSB biofertilizer mixture in the SRS from the mushroom production reduced at least 25% of N and P chemical fertilizers for gaining the maximal seed yield and enriched soil characteristics for the sustainable black sesame cultivation in the dyked AS.

The potential for using aerated steam to eradicate strawberry mite and two-spotted spider mite on strawberry transplants.

In this study, we investigated if a steam treatment program used to produce disease-free strawberry transplants has the potential to also eliminate strawberry mite (Phytonemus pallidus) and two-spotted spider mite (Tetranychus urticae). Crowns of strawberry plants collected in a commercial field, containing young, folded leaves with all life stages of P. pallidus, and strawberry leaf discs on water agar with T. urticae with non-diapausing adult females and eggs from a laboratory rearing, were exposed to warm aerated steam in a steam cabinet in a series of four experimental runs over 2 years. The steam treatments constituted of a 1-h pre-treatment with 37 °C steam followed by a 1-h recovery period at 21-25 °C, and then a main steam treatment at 44 °C for either 2, 4 (both P. pallidus and T. urticae) or 6 h (the more heat tolerant T. urticae only). After steaming, the plant material with P. pallidus or T. urticae were incubated at 21-25 °C until survival was assessed after 1-6 days, depending on the mite species and life-stage. Non-steamed plant material with mites was used as controls. The 4-h treatment killed all P. pallidus eggs, larvae and adults, and the 2-h treatment killed all individuals in all three stages except for one egg in one of the runs. There were no or minor effects of the steam treatments on T. urticae adult and egg survival. Based on these results, the tested steam treatments may be used to eliminate the strawberry mite but not the two-spotted spider mite from strawberry planting material.

Body mass index, body fat percentage, and visceral fat as mediators in the association between health literacy and hypertension among residents living in rural and suburban areas.

Background: Hypertension is a major cause of death and disability worldwide. Enhancing health literacy (HL) may help to alleviate the risk of hypertension and its burden. However, evidence on the association between HL and hypertension and potential mechanisms remain to be explored. Objectives: This study examined the association between HL and hypertension; and explored whether body mass index (BMI), body fat percentage (PBF), and visceral fat (VF) were mediators of this association in people who resided in rural and suburban areas in Vietnam. Methods: A cross-sectional survey was conducted from 1st July to 31st December 2019, involving 1655 residents and exploring participants' sociodemographic characteristics, HL, health-related behaviors, comorbidities, body composition, and blood pressure (BP). People with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or using antihypertensive medication were classified as having hypertension. Multiple logistic regression and mediation analyses were used to explore associations. Results: The hypertension prevalence was 41.9% (694/1,655). In adjusted models, a higher HL score was associated with a lower hypertension likelihood (OR = 0.96; 95%CI = 0.95-0.97; p < 0.001). Factors associated with a higher odd of hypertension were overweight/obese (OR = 1.69; 95%CI = 1.24-2.29; p = 0.001), high PBF (OR = 2.35; 95%CI = 1.85-2.99; p < 0.001), and high VF (OR = 2.27; 95%CI = 1.63-3.16; p < 0.001). Notably, PBF significantly mediated the association between HL and hypertension (indirect effect, OR = 0.99; 95%CI = 0.98-0.99; p = 0.009; percent mediated = 8.56%). The mediating roles of BMI and VF were not found. Conclusion: The prevalence of hypertension was relatively high. People with better HL were less likely to have hypertension. The association between HL and hypertension was partially explained by PBF. Strategic approaches are required to improve people's HL and body fat which further help to manage hypertension in rural and suburban areas.

Charge-Converting Nanoemulsions as Promising Retinal Drug and Gene Delivery Systems.

AIM: This study aimed to develop phosphatase-responsive ζ potential converting nanocarriers utilizing polyphosphate-coated cell-penetrating peptide (CPP)-decorated nanoemulsions (NEs) as a novel gene delivery system to retinal cells. METHODS: Poly-l-lysine (PLL) was first conjugated with oleylamine (OA) only at its carboxylic end to form the amphiphilic PLL-oleylamine (PLOA) conjugate. Afterward, NEs were loaded with PLOA prior to being coated with tripolyphosphate (TPP) to generate PLOA/TPP NEs. A plasmid containing a reporter gene for green fluorescent protein plasmid (pGFP) was complexed with cationic surfactants forming hydrophobic ion pairs that were loaded in the oily core of NEs. Phosphate removal, ζ potential conversion, and cytotoxicity of the system were evaluated. Cellular uptake and transfection efficiency were investigated in 661W photoreceptor-like cells via microscopic analysis, fluorescence spectroscopy, and flow cytometry. RESULTS: Dephosphorylation of PLOA/TPP NEs triggered by alkaline phosphatase (ALP) resulted in the exposure of positive amine groups on the surface of NE droplets and a notable conversion of the ζ potential from -22.4 to +8.5 mV. Cellular uptake of PLOA/TPP NEs performed on 661W photoreceptor-like cells showed a 3-fold increase compared to control NEs. Furthermore, PLOA/TPP NEs also showed low cytotoxicity and high transfection efficacy with ∼50% of cells transfected. CONCLUSIONS: Polyphosphate-coated CPP-decorated NEs triggered by ALP could be a promising nanosystem to efficiently deliver drugs and genetic materials to photoreceptor-like cells and other retinal cells for potential treatments of retinal diseases.

Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer.

We have previously demonstrated the in vivo chemopreventive efficacy of flavokawain A (FKA), a novel chalcone from the kava plant, in prostate carcinogenesis models. However, the mechanisms of the anticarcinogenic effects of FKA remain largely unknown. We evaluated the effect of FKA on prostate tumor spheroid formation by prostate cancer stem cells, which were sorted out from CD44+/CD133+ prostate cancer cells 22Rv1 and DU145. FKA treatment significantly decreased both the size and numbers of the tumor spheroids over different generations of spheroid passages. In addition, the dietary feeding of FKA-formulated food to Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice bearing CD44+/CD133+ 22Rv1 xenograft tumors resulted in a significant reduction of tumor growth compared to those fed with vehicle control food-fed mice. Furthermore, the expression of stem cell markers, such as Nanog, Oct4, and CD44, were markedly downregulated in both tumor spheroids and tumor tissues. We also observed that FKA inhibits Ubc12 neddylation, c-Myc, and keratin-8 expression in both CD44+/CD133+ prostate tumor spheroids and xenograft tumors. Our results suggest that FKA can reduce the tumor-initiating properties and stemness of prostate cancer, which provides a new mechanism for the chemoprevention efficacy of FKA.

Synthesis and evaluation of sulfosuccinate-based surfactants as counterions for hydrophobic ion pairing.

Hydrophobic ion pairing is a promising strategy to raise the lipophilic character of therapeutic peptides and proteins. In past studies, docusate, an all-purpose surfactant with a dialkyl sulfosuccinate structure, showed highest potential as hydrophobic counterion. Being originally not purposed for hydrophobic ion pairing, it is likely still far away from the perfect counterion. Thus, within this study, docusate analogues with various linear and branched alkyl residues were synthesized to derive systematic insights into which hydrophobic tail is most advantageous for hydrophobic ion pairing, as well as to identify lead counterions that form complexes with superior hydrophobicity. The successful synthesis of the target compounds was confirmed by FT-IR, 1H-NMR, and 13C-NMR. In a screening with the model protein hemoglobin, monostearyl sulfosuccinate, dioleyl sulfosuccinate, and bis(isotridecyl) sulfosuccinate were identified as lead counterions. Their potential was further evaluated with the peptides and proteins vancomycin, insulin, and horseradish peroxidase. Dioleyl sulfosuccinate and bis(isotridecyl) sulfosuccinate significantly increased the hydrophobicity of the tested peptides and proteins determined as logP or lipophilicity determined as solubility in 1-octanol, respectively, in comparison to the gold standard docusate. Dioleyl sulfosuccinate provided an up to 8.3-fold higher partition coefficient and up to 26.5-fold higher solubility in 1-octanol than docusate, whereas bis(isotridecyl) sulfosuccinate resulted in an up to 6.7-fold improvement in the partition coefficient and up to 44.0-fold higher solubility in 1-octanol. The conjugation of highly lipophilic alkyl tails to the polar sulfosuccinate head group allows the design of promising counterions for hydrophobic ion pairing. STATEMENT OF SIGNIFICANCE: Hydrophobic ion pairing enables efficient incorporation of hydrophilic molecules into lipid-based formulations by forming complexes with hydrophobic counterions. Docusate, a sulfosuccinate with two branched alkyl tails, has shown highest potential as anionic hydrophobic counterion. As it was originally not purposed for hydrophobic ion pairing, its structure is likely still far away from the perfect counterion. To improve its properties, analogues of docusate with various alkyl tails were synthesized in the present study. The investigation of different alkyl residues allowed to derive systematic insights into which tail structures are most favorable for hydrophobic ion pairing. Moreover, the lead counterions dioleyl sulfosuccinate and bis(isotridecyl) sulfosuccinate bearing highly lipophilic alkyl tails provided a significant improvement in the hydrophobicity of the resulting complexes.

Skin optical properties in the obese and their relation to body mass index: a review.

SIGNIFICANCE: Obesity is a worldwide epidemic contributing directly to several cardiovascular risk factors including hypertension and type 2 diabetes. Wearable devices are becoming better at quantifying biomarkers relevant for the management of health and fitness. Unfortunately, both anecdotal evidence and recent studies indicate that some wearables have higher levels of error when utilized by populations with darker skin tones and high body mass index (BMI). There is an urgent need for a better evaluation of the limits of wearable health technologies when used by obese individuals. AIMS: (1) To review the current know-how on changes due to obesity in the skin epidermis, dermis, and subcutis that could affect the skin optical properties; (2) for the green wavelength range, to evaluate the difference in absorption and scattering coefficients from the abdominal skin between individuals with and without elevated BMI. The changes include alterations in layer thickness and cell size, as well as significant differences in chromophores and scatterer content, e.g., water, hemoglobin, collagen, and lipids. APPROACH: We have summarized literature pertaining to changes in skin and its components in obesity and report the results of our search using articles published between years 1971 and 2020. A linear model was used to demonstrate the absorption and reduced scattering coefficient of the abdominal skin of individuals with and without elevated BMI in the green wavelength range (530 to 550 nm) that is typically found in most wearables. RESULTS: The general trends indicate a decrease in absorption for both dermis and subcutis and an increase in reduced scattering for both epidermis and dermis. At 544-nm wavelength, a typical wavelength used for photoplethysmography (PPG), the absorption coefficient's relative percentage difference between high and low BMI skin, was 49% in the subcutis, 19% in the dermis, and negligible in the epidermis, whereas the reduced scattering coefficient relative difference was 21%, 29%, and 165% respectively. CONCLUSIONS: These findings suggest that there could be significant errors in the output of optical devices used for monitoring health and fitness if changes due to obesity are not accounted for in their design.

Polyaminated pullulan, a new biodegradable and cationic pullulan derivative for mucosal drug delivery.

AIM: To prepare new polycationic pullulan derivatives exhibiting highly mucoadhesive and sustained drug release properties. METHODS: Hydroxy groups of pullulan were activated with mesyl chloride followed by conjugation with low-molecular weight polyamines. Pullulan-tris(2-aminoethyl)amine (Pul-TAEA) and pullulan-polyethyleneimine (Pul-PEI) were evaluated regarding swelling behaviour, mucoadhesive properties and potential to control drug release. RESULTS: Pul-TAEA and Pul-PEI exhibited excellent swelling properties at pH 6.8 showing 240- and 370-fold increase in weight. Compared to unmodified pullulan, Pul-TAEA and Pul-PEI displayed 5- and 13.3-fold increased dynamic viscosity in mucus. Mucoadhesion studies of Pul-TAEA and Pul-PEI on intestinal mucosa showed a 6- and 37.8-fold increase in tensile strength, and a 72- and 120-fold increase in mucoadhesion time compared to unmodified pullulan, respectively. Due to additional ionic interactions between cationic groups on polyaminated pullulans and an anionic model drug, a sustained drug release was achieved. CONCLUSIONS: Polyaminated pullulans are promising novel mucoadhesive excipients for mucosal drug delivery.