3D-Bioprinted Skin Tissues for Improving Wound Healing: Current Status and Perspective.

Advancements in tissue engineering enable the fabrication of complex and functional tissues or organs. In particular, bioprinting enables controlled and accurate deposition of cells, biomaterials, and growth factors to create complex 3D skin constructs specific to a particular individual. Despite these advancements, challenges such as vascularization, long-term stability, and regulatory considerations hinder the clinical translation of bioprinted skin constructs. This chapter focuses on such approaches using advanced biomaterials and bioprinting techniques to overcome the current barriers in wound-healing studies. Moreover, it addresses current obstacles in wound-healing studies, highlighting the need for continued research and innovation to overcome these barriers and facilitate the practical utilization of bioprinted skin constructs in clinical settings.

Chemoprotective effect of arbutin on azoxymethane-induced aberrant crypt foci in rat colon via modulation of PCNA/Bax protein.

Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.

A Novel Cyclin-Dependent Kinase 13 Variant and Unusual Association of Situs Inversus Partialis in a Child From Bahrain: A Case Report and Literature Review.

Cyclin-dependent kinase 13 (CDK13)-related disorder is a rare autosomal dominant disease caused by pathogenic variants in the CDK13 gene. This disorder was found to be related to several clinical features, including structural cardiac anomalies, developmental delay, anomalies of the corpus callosum, and a variety of facial dysmorphisms. In addition, feeding difficulties and neonatal hypotonia might also present. The diagnosis of this disorder is based on molecular genetic testing to detect the causative pathogenic variants. Here, we report a case of a one-year-old girl from Yemen, residing in Bahrain, with a CDK13-related disorder who was found to have an unusual association of abdominal situs inversus along with multiple structural cardiac anomalies, including atrial septal defect, ventricular septal defect, patent ductus arteriosus, interrupted inferior vena cava, bilateral superior vena cava, mild coarctation of the aorta, dilated coronary sinuses, and mild regurgitation in the tricuspid valve. Moreover, facial dysmorphism including medial epicanthal folds, posteriorly rotated ears, and a depressed nasal bridge was also noted. Further assessment showed a delay in reaching developmental milestones, including speech and motor delay. The patient also presented with recurrent episodes of upper respiratory tract infections, acute bronchiolitis, and lobar pneumonia which required admission to the intensive care unit and ventilation. The last infection episode was at the age of one year. Thereafter, the patient underwent cardiac repair of the ventricular septal defect followed by no more infection episodes until the age of one year and two months. The diagnosis of CDK13 was confirmed by a whole exome sequencing test which demonstrated a novel missense variant in exon 14 of the CDK13 gene as a variant of uncertain significance in a heterozygous state.

Micro-shear bond strength of a novel resin-modified glass ionomer luting cement (eRMGIC) functionalized with organophosphorus monomer to different dental substrates.

Objectives: This study aims to assess and compare the micro-shear bond strength (µSBS) of a novel resin-modified glass-ionomer luting cement functionalized with a methacrylate co-monomer containing a phosphoric acid group, 30 wt% 2-(methacryloxy) ethyl phosphate (2-MEP), with different substrates (dentin, enamel, zirconia, and base metal alloy). This assessment is conducted in comparison with conventional resin-modified glass ionomer cement and self-adhesive resin cement. Materials and methods: In this in vitro study, ninety-six specimens were prepared and categorized into four groups: enamel (A), dentin (B), zirconia (C), and base metal alloys (D). Enamel (E) and dentin (D) specimens were obtained from 30 human maxillary first premolars extracted during orthodontic treatment. For zirconia and metal alloys, 48 disks were manufactured using IPS e.max ZirCAD through dry milling and Co-Cr powder alloy by selective laser milling. Each group was further subdivided into three subgroups (n = 8) according to the luting cement used: (1) Fuji PLUS resin-modified glass ionomer luting cement (FP) as a control cement, (2) modified control cement (eRMGIC), and (3) RelyX U 200 (RU 200) self-adhesive resin cement. The two-way analysis of variance and Tukey's HSD were used to assess the data obtained from measuring the µSBS of the samples. Results: The results of this study showed that the mean µSBS values of eRMGIC were statistically higher compared to FP in all tested groups (p < 0.001). The mean µSBS results of eRMGIC were non-significantly different from those recorded by RU 200 for all substrates except for the dentin substrate, where the RU200 cement produced significantly higher strength (p < 0.001). The failure modes were limited to a combination of mixed and adhesive failures without pure cohesive failure. Significance: The functionalization of FP with an organophosphorus co-monomer (2-MEP) directly affects the adhesion performance of the functionalized cement, which may be utilized to develop a new type of acid-base cement. It exhibited a performance comparable to that of resin-based cement and should serve well under different clinical conditions.

Tuning into miRNAs: A comprehensive analysis of their impact on diagnosis, and progression in asthma.

Asthma is a diverse inflammatory illness affecting the respiratory passages, leading to breathing challenges, bouts of coughing and wheezing, and, in severe instances, significant deterioration in quality of life. Epigenetic regulation, which involves the control of gene expression through processes such as post-transcriptional modulation of microRNAs (miRNAs), plays a role in the evolution of various asthma subtypes. In immune-mediated diseases, miRNAs play a regulatory role in the behavior of cells that form the airway structure and those responsible for defense mechanisms in the bronchi and lungs. They control various cellular processes such as survival, growth, proliferation, and the production of chemokines and immune mediators. miRNAs possess chemical and biological characteristics that qualify them as suitable biomarkers for diseases. They allow for the categorization of patients to optimize drug selection, thus streamlining clinical management and decreasing both the economic burden and the necessity for critical care related to the disease. This study provides a concise overview of the functions of miRNAs in asthma and elucidates their regulatory effects on the underlying processes of the disease. We provide a detailed account of the present status of miRNAs as biomarkers for categorizing asthma, identifying specific asthma subtypes, and selecting appropriate treatment options.

Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurological disorder characterized by the impairment of the motor system, resulting in symptoms such as resting tremor, cogwheel rigidity, bradykinesia, difficulty with gait, and postural instability. The occurrence of striatal dopamine insufficiency can be attributed to a notable decline in dopaminergic neurons inside the substantia nigra pars compacta. Additionally, the development of Lewy bodies serves as a pathological hallmark of PD. While current therapy approaches for PD aim to preserve dopaminergic neurons or replenish dopamine levels in the brain, it is important to acknowledge that achieving complete remission of the condition remains elusive. MicroRNAs (miRNAs, miR) are a class of small, non-coding ribonucleic acids involved in regulating gene expression at the post-transcriptional level. The miRNAs play a crucial part in the underlying pathogenic mechanisms of several neurodegenerative illnesses, including PD. The aim of this review is to explore the role of miRNAs in regulating genes associated with the onset and progression of PD, investigate the potential of miRNAs as a diagnostic tool, assess the effectiveness of targeting specific miRNAs as an alternative therapeutic strategy to impede disease advancement, and discuss the utilization of newly developed nanoparticles for delivering miRNAs as neurodegenerative therapies.

Multifocal lesions in a kidney allograft.

BACKGROUND: Common complications following kidney transplant include infection, rejection, and malignancy. Multiple masses in a transplanted kidney raise suspicion for malignancy. CASE PRESENTATION: A 20-year-old female with chronic kidney disease stage 3 T presented with graft tenderness, acute kidney injury, and heterogeneous masses in her transplanted kidney visualized via ultrasound. She was inadequately treated for chlamydia 1 month prior and retested positive upon admission. Initial workup revealed anemia, hyperglycemia, hyperuricemia, and elevated lactate dehydrogenase. Magnetic resonance imaging revealed complex masses of varying sizes in the transplanted kidney. Biopsy grew Streptococcus agalactiae, informing the diagnosis of multiple perinephric abscesses. Additional evaluations for infectious etiology were unremarkable. Her perinephric abscesses resolved with several months of antibiotics. CONCLUSIONS: Even without a clear source, serious infections may develop in kidney transplant patients who otherwise have concern for malignancy. Chlamydial infections may lead to serious intra-abdominal infections in immunocompromised patients. The inadequately treated chlamydia likely led to polymicrobial ascension of the genitourinary tract that seeded the transplanted kidney. A high index of suspicion for infection is essential in immunosuppressed patients. Biopsy is crucial for a timely diagnosis.

Green synthesized silver nanoparticles using the plant-based reducing agent Matricaria chamomilla induce cell death in colorectal cancer cells.

OBJECTIVE: There is a need to treat cancer cells with safe and natural nanoparticles to avoid the side effects of chemotherapeutic agents. Chamomile is considered a safe, natural plant with anticancer activity. We synthesize simple, inexpensive, and eco-friendly silver nanoparticles (SNs) using Chamomile (CHM) to tune their anticancer properties. MATERIALS AND METHODS: SN-CHM was synthesized by reducing 1 mM silver nitrate aqueous solution in 100 mL with the aqueous ethanolic flower extract of CHM (18 mg/mL, w/v). The reaction proceeded overnight at 600 rpm and 28°C. SN-CHM was characterized for their % yield, average diameter, charge, morphology, and silver release. Moreover, SN-CHM was investigated for its antioxidant and anticancer activities at 200 µg/mL and 5 mg/ mL, respectively. RESULTS: A 59.12% yield and a uniform SN-CHM size of 115 ± 3.1 nm with a ζ-potential of -27.67 ± (-3.92) mv were observed. The UV-visible absorption showed shifts from 379.5 to 383.5 nm for CHM and SN-CHM, respectively. Moreover, Ag+ was ultimately released from SN-CHM after 5 h. Fourier Transform Infrared Spectroscopy (FT-IR) showed characteristic absorption peaks of CHM and produced SN-CHM. Furthermore, SN-CHM showed moderate antioxidant activity. SN-CHM inhibited the % viability of SW620 and HT-29 cell lines at 20 µM. SN-CHM may also greatly upregulate the apoptotic gene BAX while considerably downregulating the anti-apoptotic genes BCL2 and BCL-Xl. CONCLUSIONS: CHM can be a safe soft drink, especially when conjugated with Ag ions as anticancer NPs. SN-CHM is considered potent anticancer activity against SW620, and HT-29 cell lines.

Assessment of the readiness and response toward the dengue fever outbreak (2019) in Sudan: a qualitative exploration.

BACKGROUND: Dengue fever (DF) is a mosquito-borne viral disease transmitted by Aedes mosquito species and has been considered a major public health problem in Kassala State for tens of years. This study aimed to assess the level of readiness and response toward the 2019 dengue fever outbreak in Kassala at the state and community levels. METHODS: This exploratory cross-sectional study was conducted in Kassala State, Sudan, from January to March 2020. The researcher conducted interviews with the key respondents at the state level to assess the level of readiness and response and to reflect the capacity of institutions-public health authorities, health systems, and emergency response bodies. RESULTS: The surveillance system reported 3961 DF cases in Kassala State, representing 93.5% of the total cases in Sudan between August 2019 and January 2020. This outbreak was identified by passive surveillance, 51 samples were tested during the outbreak period, and private clinics and labs were not included in the surveillance system. According to the WHO checklist of outbreak readiness and response, Kassala's surveillance system and public health laboratory received the lowest scores. CONCLUSIONS: The study concludes that outbreak readiness and response could be considered below standards, mainly in the surveillance system and laboratory diagnostic facilities, due to the absence of intersectoral collaboration with a regulatory framework in terms of financial and operational participation.

Marginal Adaptation and Fracture Resistance of 3D Printed and CAD/CAM Milled Definitive Resin Matrix Ceramic Crowns.

AIM: To evaluate and compare the marginal adaptation and fracture resistance of resin matrix ceramic crowns fabricated using 3-dimensional (3D) printing and computer aided design/computer aided manufacturing (CAD/CAM) milling technology. MATERIALS AND METHODS: Thirty extracted human maxillary first premolars were prepared to receive crown restorations and grouped into 3 groups according to 3 different crown materials (n = 10): VE: teeth restored with milled Vita Enamic, CS: teeth restored with milled Cerasmart 270 and VSC: teeth restored with 3D-printed VarseoSmile Crown Plus. Marginal analysis was performed with the aid of a digital microscope at (230x) magnification, both before and after cementation with self-adhesive resin cement and analyzed with Image J analysis software. The fracture loads for each sample were then recorded using a universal testing machine in a single load-to-failure test up until the crowns failed. RESULTS: The lowest marginal gap values were recorded for VSC before (8.03 µm) and after (15.07 µm) cementation with significant difference compared to the other crown materials (p <0.05), while the differences between the milled groups were non-significant both before, (CS (11.35 µm) and VE (11.86 µm)), and after cementation, (CS (20.01 µm) and VE (21.08 µm)). In terms of fracture resistance, VE recorded significantly lower fracture load values (727.8 N) (p <0.05) than the crowns fabricated from CS (1213.8 N) and VSC (1181.5 N), which showed no statistically significant differences between each other. CONCLUSION: 3D printed definitive crowns outperformed CAD/CAM milled crowns in terms of marginal adaptation, along with comparable fracture resistance values.

Dapagliflozin improves early acute kidney injury induced by vancomycin in rats: Insights on activin A/miRNA-21 signaling and FOXO3a expression.

Drug-induced acute kidney injury (AKI) represents a potentially serious disorder associated with increased morbidity and mortality. The presented study investigated the ability of the oral antidiabetic agent, dapagliflozin (DAPA), to preserve the kidneys of rats subjected to vancomycin (VCM)-induced AKI. Rats were injected with VCM (400 mg/kg; i.p daily) for 7 successive days to induce AKI. Rats that received VCM were pretreated with DAPA at 5 or 10 mg/kg; p.o daily for 14 successive days. Vancomycin-treated rats depicted renal tubular damage, decline in renal function, and renal morphological alterations. Impairment of renal antioxidant machinery and propagation of renal cell apoptosis was apparent in the setting of VCM overdose. Pretreatment of VCM rats with DAPA, particularly at 10 mg/kg, effectively attenuated NADPH oxidase-4 (NOX4)-induced renal ROS, hampered activin A activation, and repressed miRNA-21/PTEN/pAKT signaling. These events were associated with impeding the expression of renal p-FOXO3a/t-FOXO3a ratio and promoting the nuclear localization of FOXO3a immnoexpression, enhancing renal antioxidant enzymes. At the same time, DAPA pretreatment improved renal function indices and alleviated the kidney injury markers, NGAL, and KIM-1, accompanied by restoring the normal renal histopathological structure. Regarding renal apoptosis, DAPA suppressed the expression of Bax/Bcl2 ratio and caspase-3. This study demonstrates that DAPA ameliorates VCM-induced AKI in rats via modulating renal oxidative stress, presumably by interfering with NOX4/activin A/miRNA-21 cascade and augmenting t-FOXO3a expression as well as dampening renal cell apoptosis.

Microplastic-sorbed persistent organic pollutants in coastal Mediterranean Sea areas of Tunisia.

Microplastics (MPs) are emerging pollutants of global concern due to their pervasiveness, high sorption ability for persistent organic pollutants (POPs) and direct and indirect toxicity to marine organisms, ecosystems, as well as humans. As one of the major coastal interfaces, beaches are considered among the most affected ecosystems by MPs pollution. The morphological characteristics of MPs (pellets and fragments) collected from four beaches along the Tunisian coast and sorbed POPs, including polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), were investigated in this study. The results showed that the MPs varied greatly in color, polymer composition and degradation degree. The color varied from colored to transparent and the most prevalent polymer identified using Raman spectroscopy was polyethylene. Scanning electron microscope (SEM) images exhibited various surface degradation features including cavities, cracks, attached diatom remains, etc. The concentrations of Σ12PCBs over all beaches ranged from 14 to 632 ng g-1 and 26 to 112 ng g-1 in the pellets and fragments, respectively, with a notable presence and dominance of highly-chlorinated PCBs such as CB-153 and -138. Among the OCPs, γ-HCH is the only compound detected with concentrations ranging from 0.4 to 9.7 ng g-1 and 0.7 to 4.2 ng g-1 in the pellets and fragments, respectively. Our findings indicate that MPs found on the Tunisian coast may pose a chemical risk to marine organisms as the concentrations of PCBs and γ-HCH in most of the analysed samples exceeded the sediment-quality guidelines (SQG), especially the effects range medium (ERM) and the probable effects level (PEL). As the first report of its kind, the information gathered in this study can serve as the baseline and starting point for future monitoring work for Tunisia and neighbouring countries, as well as for stakeholders and coastal managers in decision-making processes.

Rodent-borne zoonoses in Qatar: A possible One-Health framework for the intervention of future epidemic.

The increasing frequency of spillover of zoonotic pathogens from animals to humans in recent years highlights a need to develop a more comprehensive framework to investigate and prevent pathogens of animal origin, including rodents. Despite the presence of several species of rodents, there is a certain knowledge gap regarding rodent-borne zoonoses in Qatar. The current review provides an update on rodent-borne zoonoses in Qatar, its possible drivers and transmission dynamics, and proposed a One Health framework for intervention. Following an extensive literature review, we conducted a field investigation. Then the qualitative information and knowledge gaps were addressed with a virtual discussion with national, regional, and international experts in the relevant field. Overall, Rattus norvegicus population was found to be more prevalent, followed by Rattus rattus, and M. musculus, which are mainly found in animal farms, followed by agricultural farms, residential areas, and other facilities. Over 50% of rodents carry at least one pathogen of public health importance. Several pathogens were identified at the human, animal, and ecosystem interface, which can be mediated in transmission by rodents. E. coli, Salmonella spp., and Campylobacter spp. are the frequently reported bacteria. Hymenolepis spp., Cryptosporidium spp., Giardia spp., Entamoeba spp., and Toxoplasma spp. are the major parasites. In addition, many vectors, including Ornithonyssus bacoti and Xenopsylla astia were reported in this country. Based on the changes over the past 70 years in Qatar, seven drivers have been identified, which could be important in rodent-borne disease emergences, such as the Oil and gas revolution, fast population growth, rapid urbanization, importation of food and agricultural products, agricultural and livestock development, farm biosecurity, and stray animals. The experts emphasized that mixed-species animal farming with poor biosecurity and management can be associated to increase the risk of zoonoses. Moreover, rapid urbanization and global climate change together can alter the ecosystem of the country and impact on vectors and vector-borne diseases. Finally, the One Health framework has been proposed for the surveillance, and mitigation of any future spillover or epidemic of rodent-borne zoonoses.

The interplay of signaling pathways and miRNAs in the pathogenesis and targeted therapy of esophageal cancer.

Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-ß signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.

Synergistic Effect of Sophora japonica and Glycyrrhiza glabra Flavonoid-Rich Fractions on Wound Healing: In Vivo and Molecular Docking Studies.

Glycyrrhiza glabra and Sophora japonica (Fabaceae) are well-known medicinal plants with valuable secondary metabolites and pharmacological properties. The flavonoid-rich fractions of G. glabra roots and S. japonica leaves were prepared using Diaion column chromatography, and the confirmation of flavonoid richness was confirmed using UPLC-ESI-MS profiling and total phenolics and flavonoids assays. UPLC-ESI-MS profiling of the flavonoid-rich fraction of G. glabra roots and S. japonica leaves resulted in the tentative identification of 32 and 23 compounds, respectively. Additionally, the wound healing potential of topical preparations of each fraction, individually and in combination (1:1) ointment and gel preparations, were investigated in vivo, supported by histopathological examinations and biomarker evaluations, as well as molecular docking studies for the major constituents. The topical application of G. glabra ointment and gel, S. japonica ointment and gel and combination preparations significantly increase the wound healing rate and the reduction of oxidative stress in the wound area via MDA reduction and the elevation of reduced GSH and SOD levels as compared to the wound and Nolaver®-treated groups. The molecular docking study revealed that that major compounds in G. glabra and S. japonica can efficiently bind to the active sites of three proteins related to wound healing: glycogen synthase kinase 3-ß (GSK3-ß), matrix metalloproteinases-8 (MMP-8) and nitric oxide synthase (iNOS). Consequently, G. glabra roots and S. japonica leaves may be a rich source of bioactive metabolites with antioxidant, anti-inflammatory and wound healing properties.

Whitish truffles found in Finland: soil characteristics, and identification based on morphological and molecular properties.

The growing demand for truffles has led to a global pursuit for their occurrence in the wild, and studies concerning their cultivation. Although European countries such as Italy, France and Spain have been known for truffle production, truffle hunting is new to Finland. The present study reports for the first time, the findings of Tuber maculatum in Finland on the basis of morphological and molecular analysis. The chemical characteristics of soil samples collected from the truffle sites have also been discussed. The species of the Tuber samples were identified primarily using morphological analysis. Molecular analysis was carried out for the confirmation of the identity of the species. Two phylogenetic trees were constructed based on internal transcribed spacer (ITS) sequences produced in this study and including representative sequences of whitish truffles available in GenBank. The truffles were identified as T. maculatum and T. anniae. This study could be considered as a basis for encouraging research on findings and identification of truffles in Finland.

Boosting the In Vivo Transdermal Bioavailability of Asenapine Maleate Using Novel Lavender Oil-Based Lipid Nanocapsules for Management of Schizophrenia.

Lipid nanocapsules (LNCs) are promising for transdermal drug delivery due to their higher permeability-enhancing effects compared to polymeric nanoparticles. Lavender oil is an essential oil consisting of several terpenes (primarily linalool and linalyl acetate) known for their profound permeation-enhancing action. In the present work, we successfully encapsulated asenapine maleate (a second-generation antipsychotic that is highly metabolized by the liver, reducing its oral bioavailability) into biocompatible LNCs for transdermal application using a novel oily phase, i.e., lavender oil (LO-LNCs). A comparative study was conducted to determine the effects of different oily phases (i.e., Miglyol® 812, Labrafil® M1944CS, and Labrafac™ PG) on the LNCs. Surfactant types (Kolliphor® HS15, Kolliphor® EL and Tween80) and oil:surfactant ratios were studied. Blank and asenapine-loaded LNCs were optimized for particle size, polydispersity index, zeta potential, drug content and ex vivo skin permeation. Lavender oil and Labrafil® showed smaller vesicular sizes, while LO-LNCs increased the permeation of ASP across rat skin. In vivo pharmacokinetics revealed that LO-LNCs could increase the ASP Cmax via transdermal application by fourfold compared to oral suspension. They increased the bioavailability of ASP by up to 52% and provided sustained release for three days. The pharmacokinetic profile of the LO-LNCs was compared to ASP-loaded invasomes (discussed in a previous study) to emphasize LNCs' transdermal delivery behavior.

Vildagliptin restores cognitive function and mitigates hippocampal neuronal apoptosis in cisplatin-induced chemo-brain: Imperative roles of AMPK/Akt/CREB/ BDNF signaling cascades.

Cisplatin (CP) is a broad-spectrum antineoplastic agent used to treat many human cancers. Nonetheless, most patients receiving CP suffer from cognitive deficits, a phenomenon termed "chemo-brain". Recently, vildagliptin (Vilda), a DPP-4 inhibitor, has demonstrated promising neuroprotective properties against various neurological diseases. Therefore, the present study aims to investigate the potential neuroprotective properties of Vilda against CP-induced neurotoxicity and elucidate the underlying molecular mechanisms. Chemo-brain was induced in Sprague-Dawley rats by i.p injection of CP at a dose of 5 mg/kg once weekly for four weeks. Vilda was administered daily at a dose (10 mg/kg; P.O) for four weeks. The results revealed that Vilda restored the cognitive function impaired by CP, as assessed by the Morris water maze, Y-maze, and passive avoidance tests. Moreover, Vilda alleviated the CP-induced neurodegeneration, as shown by toluidine blue staining, besides markedly reduced amyloid plaque deposition, as evidenced by Congo red staining. Notably, Vilda boosted cholinergic neurotransmission through the downregulation of the acetylcholinesterase enzyme. In addition, the neuroprotective mechanisms of Vilda include diminishing oxidative stress by reducing MDA levels while raising GSH levels and SOD activity, repressing neuronal apoptosis as shown by elevated Bcl-2 levels together with diminished Bax and caspase-3 expressions, inhibiting neuroinflammation as shown by decreased GFAP expression, and finally boosting hippocampal neurogenesis and survival by upregulating expressions of BDNF and PCNA. These effects were mainly mediated by activating AMPK/Akt/CREB signaling cascades. In summary, Vilda can be considered a promising candidate for guarding against CP-induced chemo-brain and neurodegeneration, thus improving the quality of life of cancer patients.

The role of miRNAs in insulin resistance and diabetic macrovascular complications - A review.

Diabetes is the most prevalent metabolic disturbance disease and has been regarded globally as one of the principal causes of mortality. Diabetes is accompanied by several macrovascular complications, including stroke, coronary artery disease (CAD), and cardiomyopathy as a consequence of atherosclerosis. The onset of type 2 diabetes is closely related to insulin resistance (IR). miRNAs have been linked to various metabolic processes, including glucose homeostasis, regulation of lipid metabolism, gluconeogenesis, adipogenesis, glucose transporter type 4 expression, insulin sensitivity, and signaling. Consequently, miRNA dysregulation mediates IR in some target organs, comprising liver, muscle, and adipose tissue. Moreover, miRNAs are crucial in developing diabetes and its associated macrovascular complications through their roles in several signaling pathways implicated in inflammation, apoptosis, cellular survival and migration, the proliferation of vascular smooth muscle cells, neurogenesis, angiogenesis, autophagy, oxidative stress, cardiac remodeling, and fibrosis. Therefore, the purpose of this review is to clarify the role of miRNAs in hepatic, muscle, and adipose tissue IR and explain their roles in the pathogenesis of macrovascular diabetic complications, including stroke, CAD, and cardiomyopathy. Also, explain their roles in gestational diabetes mellitus (GDM). Besides, this review discusses the latest updates on the alteration of miRNA expression in diabetic macrovascular complications.

Assessment of fluid removal using ultrasound, bioimpedance and anthropometry in pediatric dialysis: a pilot study.

BACKGROUND: Fluid overload is associated with morbidity and mortality in children receiving dialysis. Accurate clinical assessment is difficult, and using deuterium oxide (D2O) to measure total body water (TBW) is impractical. We investigated the use of ultrasound (US), bioimpedance spectroscopy (BIS), and anthropometry to assess fluid removal in children receiving maintenance hemodialysis (HD). METHODS: Participants completed US, BIS, and anthropometry immediately before and 1-2 h after HD for up to five sessions. US measured inferior vena cava (IVC) diameter, lung B-lines, muscle elastography, and dermal thickness. BIS measured the volume of extracellular (ECF) and intracellular (ICF) fluid. Anthropometry included mid-upper arm, calf and ankle circumferences, and triceps skinfold thickness. D2O was performed once pre-HD. We assessed the change in study measures pre- versus post-HD, and the correlation of change in study measures with percent change in body weight (%∆BW). We also assessed the agreement between TBW measured by BIS and D2O. RESULTS: Eight participants aged 3.4-18.5 years were enrolled. Comparison of pre- and post-HD measures showed significant decrease in IVC diameters, lung B-lines, dermal thickness, BIS %ECF, mid-upper arm circumference, ankle, and calf circumference. Repeated measures correlation showed significant relationships between %∆BW and changes in BIS ECF (rrm =0.51, 95% CI 0.04, 0.80) and calf circumference (rrm=0.80, 95% CI 0.51, 0.92). BIS TBW correlated with D2O TBW but overestimated TBW by 2.2 L (95% LOA, -4.75 to 0.42). CONCLUSION: BIS and calf circumference may be helpful to assess changes in fluid status in children receiving maintenance HD. IVC diameter, lung B-lines and dermal thickness are potential candidates for future studies.