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.

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.

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.

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.

Safety of artemisinins during early pregnancy, assessed in 62 Sudanese women.

Between June 2006 and October 2008, the safety of artemisinins during early human pregnancy was assessed in central-eastern Sudan. Pregnant women in the first or second trimester who were attending antenatal-care clinics at the Wad Medani, Gadarif and New Halfa hospitals were interviewed. Each was asked if they had had malaria in the first trimester of the index pregnancy and, if so, what treatment they had received. The women who had received artemisinins were then followed-up until delivery and their babies were followed-up until they were 1-year-olds. Overall, 62 of the pregnant women reported receiving artemisinins - artemether injections (48), artesunate plus sulfadoxine-pyrimethamine (11) or artemether plus lumefantrine (three) - during the first trimester. Medical records were available for 51 (82%) of these 62 women, and, in each case, these records showed the reported treatment and that malaria had been confirmed. Only nine (15%) of the 62 women given artemisinins had not known that they were pregnant when treated. Two of the treated women (both given artemether injections in the first trimester) had miscarriages, one at 20 weeks of gestation and the other at 22 weeks, each while receiving quinine infusions for a second attack of malaria. The other 60 women who had received artemisinins delivered apparently healthy babies at full term. No congenital malformations were detected, there was no preterm labour, no maternal deaths were recorded during the follow-up, and none of the babies died during their first year of life. It therefore appears that artemisinins may be safe to use during early pregnancy, although further study is clearly needed.

Cytodiagnosis of nipple discharge: a study of 602 samples from 484 cases.

To find out the gross and microscopic differentiating features between nipple discharges (ND) due to various breast lesions, smears of 602 ND samples from 484 cases were reviewed by one of the investigators (D.K.D.). The reviewed cytodiagnoses were as follows: benign nipple discharge (59.1%), inflammatory ND (6.5%), ?papillary lesions (2.5%), papillary lesions (20.6%), papillary lesions with atypia (3.8%), duct cells with atypia (0.2%), suspicious for malignancy (0.5%), malignant ND (1.2%), and inadequate (5.6%). Following review, samples with epithelial abnormalities (?papillary lesion, papillary lesion with and without atypia, duct cells with atypia, suspicious for malignancy, and malignancy) increased from 16.6% to 30.4% of adequate samples (P < 0.0001). 37.9% unilateral ND samples showed epithelial abnormalities, as opposed to 18.9% of bilateral ND samples (P < 0.0001). Bloodstained ND showed epithelial abnormalities in 41.5% samples, as compared to 22.1% of ND with other specified gross characteristics (P < 0.0001). The samples with epithelial abnormalities differed significantly from benign and inflammatory ND in respect of frequency of benign duct cells, duct cells with atypia, papillary clusters with or without atypia, malignant cells, columnar cells, red blood cells, inflammatory cells, and background lipid vacuoles (P < 0.01 to < 0.0001). The ND samples with suspicious and malignant cytology, besides the presence of malignant cells (P < 0.0001), differed significantly from rest of the lesions in respect of foam cells (P < 0.0001), red blood cells (P < 0.01), and inflammatory cells (P < 0.05). When compared with histopathological diagnosis in 20 cases, the benign or malignant nature of the lesion was correctly identified in ND in 80% cases. The ND cytologies in 7 histologically proved malignant cases were malignancy (3 cases), suspicious for malignancy (1 case), papillary lesion with atypia (1 case), papillary lesion (1 case), and benign ND (1 case).

Fine needle aspiration biopsy of azoospermic testes. Could it replace histologic biopsy?

OBJECTIVE: To evaluate the possibility of replacing histologic biopsy of azoospermic testes by fine needle aspiration (FNA) for diagnostic and management purposes. STUDY DESIGN: Twenty-seven patients were examined under general anesthesia, and 53 testes were biopsied by FNA. Fifty-four testes were biopsied for histologic examination. Histology and cytology of each testis were compared to assess the discrepancy or concordance between the diagnoses. RESULTS: Twenty-seven testes showed complete concordance of cytology and histology, and 13 testes showed a mild degree of discrepancy. A severe degree of discrepancy was seen in 13 testes. In the majority of discrepant cases, FNA biopsy diagnosis was more sensitive in detecting evidence of full or advanced maturation. In one case of discrepancy, the histologic finding was Sertoli cells only, and cytology revealed focal full maturation. In vitro fertilization using sperm from this case was successful. CONCLUSION: FNA biopsy of testes in azoospermia is a fast, reliable and minimally traumatic method. The prospects for utilizing FNA biopsy material in assisted and microassisted fertilization are promising.

Detection of Schistosoma mansoni in bronchoalveolar lavage fluid. A case report.

BACKGROUND: Bronchoalveolar lavage (BAL) is a useful tool in the diagnosis of bacterial, viral, fungal and parasitic pulmonary infections. There have been rare reports of parasitic infestations in bronchoalveolar lavage fluid. This is the first case report on detecting a Schistosoma ova in BAL fluid. CASE: A 40-year-old, Egyptian male presented with a fever and productive cough. He had a right pleural effusion and segmental collapse of the right lower lobe. BAL fluid showed several ova of Schistosoma mansoni and established the diagnosis of schistosomiasis. Abdominal ultrasound revealed mild hepatic cirrhosis. CONCLUSION: Schistosomiasis should be considered in the differential diagnosis of pulmonary problems in patients with disseminated disease in endemic areas.

Preparation of void-free casts from vinyl polysiloxane impressions.

PURPOSE: To investigate two techniques to produce void-free casts from vinyl polysiloxane impressions. MATERIALS AND METHODS: Thirty casts prepared using a conventional technique were compared with 30 casts prepared using a technique involving syringing of stone in terms of numbers of surface voids. RESULTS: Significantly fewer surface voids were observed in the casts prepared using syringing technique. CONCLUSION: The syringing technique investigated is considered to have advantages over the conventional technique for the production of casts from vinyl polysiloxane impressions.

Loperamide in acute diarrhoea in childhood: results of a double blind, placebo controlled clinical trial.

Fifty-three young children with acute diarrhoea were included in a hospital-based, double-blind trial of loperamide at two dose levels (0.4 and 0.8 mg/kg/day), given with standard oral rehydration therapy versus placebo plus oral rehydration therapy. The differences in the overall recovery rate were significant (P less than 0.05), the fastest being in the group given 0.8 mg/kg and slowest in the placebo group. Comparison between weights on admission and weights by day 3 showed that more children in the loperamide groups gained weight than in the placebo group (P less than 0.05). No serious side effects of loperamide were observed. The drug was withdrawn in one child because of excessive lethargy and sleep. The results indicate that loperamide in the doses employed is safe and may be a useful adjunct to oral rehydration in certain children.

Loss and regeneration of the microvilli of human placental syncytiotrophoblast.

In order to explore the functional role of microvilli of the syncytiotrophoblast of the human full-term placenta, 16 placentas were examined by scanning electron microscopy (SEM). Our results showed that the microvilli projecting from the apical portion of the syncytiotrophoblast appeared to be highly pleomorphic and showed regional variations in their distribution. This has been correlated to the difference in the stage of growth of microvilli following certain obvious examples of loss. Such a process of distortion and renewal or regeneration may suggest a dynamic functional activity of the microvilli on the villous surface.

Distribution and ultrastructural characterization of the stroma in scirrhous 'infiltrating' carcinoma of the human breast.

A combination of light microscopic, histochemical, immunohistochemical and transmission electron microscopic techniques were used to study the distribution and ultrastructural characterization of the stroma of Scirrhous 'infiltrating' carcinoma of the human breast. Both the light and electron microscopic techniques emphasized the presence of regional variations in the distribution of fibrous tissue in this type of tumour. Whilst fibronectin and collagen type III appeared relatively rich in both periductal and diffused regions, there was a clear contrast in the distribution of collagen type I and elastic tissue between the two regions. Collagen type I was more numerous in the diffused regions whereas elastic tissue was more produced in the periductal regions. The present study confirmed the views that Scirrhous carcinoma cells secrete inappropriately the majority of collagen, elastic and possibly other fibrillar elements of the connective tissue stroma. Fibroblasts, myofibroblasts and myoepithelial cells are believed to contribute in a minor way to the production of the various connective tissue elements. Finally, our findings have been discussed in relation to the mechanism of invasiveness of the tumour cells.

Tropical pyomyositis in Saudi Arabia.

Tropical pyomyositis is a disease of skeletal muscle characterised by single or multiple abscesses with Staphylococcus aureus the most commonly isolated organism. Most cases have been reported from the hot and humid tropics. This report reviews the literature, describes a case from hot, dry Saudi Arabia and suggests that such cases may be missed because local clinicians may be unaware of the existence of such a clinical entity.