Search

miRNAs are non-coding RNA sequences of approximately 22 nucleotides that interact with genes by inhibiting their translation through binding to their 3' or 5' UTR regions. Following their discovery, the role they play in the development of various pathologies, particularly cancer, has been studied. In this context, miR-7 is described as an important factor in the development of cancer because of its role as a tumor suppressor, regulating a large number of genes involved in the development and progression of cancer. Recent data support the function of miR-7 as a prognostic biomarker in cancer, and miR-7 has been proposed as a strategy in cancer therapy. In this work, the role of miR-7 in various types of cancer is reviewed, illustrating its regulation, direct targets, and effects, as well as its possible relationship to the clinical outcome of cancer patients.

Members of the Bcl-2 family are proteins that play an essential role in the regulation of apoptosis, a crucial process in development and normal physiology in multicellular organisms. The essential mechanism of this family of proteins is given by the role of pro-survival proteins, which inhibit apoptosis by their direct binding with their counterpart, the effector proteins of apoptosis. This family of proteins was named after the typical member Bcl-2, which was named for its discovery and abnormal expression in B-cell lymphomas. Subsequently, the structure of one of its members BCL-xL was described, which allowed one to understand much of the molecular mechanism of this family. Due to its role of BCL-xL in the regulation of cell survival and proliferation, it has been of great interest in its study. Due to this, it is important to research its role regarding the development and progression of human malignancies, especially in hematologic malignancies. Due to its variation in expression in cancer, it has been suggested that BCL-xL can or cannot play a role in cancer depending on the cellular or tissue context. This review discusses recent advances in its transcriptional regulation of BCL-xL, as well as the advances regarding the activities of BCL-xL in hematological malignancies, its possible role as a biomarker, and its possible clinical relevance in these malignancies.

A large collection of transgenic tomato lines, each ectopically expressing a different Arabidopsis thaliana transcription factor, was screened for variants with alterations in leaf starch. Such lines may be affected in carbon partitioning, and in allocation to the sinks. We focused on ‘L4080’, which harbored an A. thaliana zDof (DNA-binding one zinc finger) isoform 1.3 (AtzDof1.3) gene, and which had a 2−4-fold higher starch-to-sucrose ratio in source leaves over the diel (p < 0.05). Our aim was to determine whether there were associated effects on productivity. L4080 plants were altered in nitrogen (N) and carbon (C) metabolism. The N-to-C ratio was higher in six-week-old L4080, and when treated with 1/10 N, L4080 growth was less inhibited compared to the wild-type and this was accompanied by faster root elongation (p < 0.05). The six-week-old L4080 acquired 42% more dry matter at 720 ppm CO2, compared to ambient CO2 (p < 0.05), while the wild-type (WT) remained unchanged. GC-MS-TOF data showed that L4080 source leaves were enriched in amino acids compared to the WT, and at 49 DPA, fruit had 25% greater mass, higher sucrose, and increased yield (25%; p < 0.05) compared to the WT. An Affymetrix cDNA array analysis suggested that only 0.39% of the 9000 cDNAs were altered by 1.5-fold (p < 0.01) in L4080 source leaves. 14C-labeling of fruit disks identified potential differences in 14-DPA fruit metabolism suggesting that post-transcriptional regulation was important. We conclude that AtzDof1.3 and the germplasm derived therefrom, should be investigated for their ‘climate-change adaptive’ potential.

The growing demand for efficient, selective, and stable enzymes has fueled advancements in computational enzyme engineering, a field that complements experimental methods to accelerate enzyme discovery. With a plethora of software and tools available, researchers from different disciplines often face challenges in selecting the most suitable method that meets their requirements and available starting data. This review categorizes the computational tools available for enzyme engineering based on their capacity to enhance the following specific biocatalytic properties of biotechnological interest: (i) protein–ligand affinity/selectivity, (ii) catalytic efficiency, (iii) thermostability, and (iv) solubility for recombinant enzyme production. By aligning tools with their respective scoring functions, we aim to guide researchers, particularly those new to computational methods, in selecting the appropriate software for the design of protein engineering campaigns. De novo enzyme design, involving the creation of novel proteins, is beyond this review's scope. Instead, we focus on practical strategies for fine-tuning enzymatic performance within an established reference framework of natural proteins. [ABSTRACT FROM AUTHOR]

Melanoma, a lethal type of cancer originating from melanocytes, is the leading cause of death among skin cancers. While surgical excision of the lesions is the primary treatment for melanoma, not all cases are candidates for surgical procedures. New treatments and complementary options are necessary, given the increasing diagnosis rate. In the present study, a norcantharidin-containing nanoemulsion was developed and evaluated in vivo using a syngeneic graft murine model. Norcantharidin is the demethylated analog of cantharidin, known for its anticancer properties. Our model contemplates surgical excision surgery simulating the standard treatment and the role of the nanoemulsion as a potential adjuvant therapy. We observed a significant decrease in the growth rate of the melanoma lesion in the treated groups compared to the control group, both at the 20th and 30th days of treatment. Moreover, we evaluated the drug bioavailability in serum samples, and the results showed that norcantharidin was detectable in a range of 0.1 to 0.18 mg/mL in the treated groups. Furthermore, histopathological analysis was performed on the amputated tumors, where significant differences were found regarding size, mitosis rate, lymphocytic infiltration, and multispectral quantitative image analysis compared to the control group. If more clinical studies are conducted, the norcantharidin-containing nanoemulsion could be a potential alternative or adjuvant therapy. Topical nanosystems can become or complement standard therapies, which is needed as melanoma affects not only in terms of mortality but also the patient's morbidity and life quality. [ABSTRACT FROM AUTHOR]

Intravaginal drug administration offers several advantages over other routes, primarily bypassing the initial stages of metabolism. Additionally, this route has demonstrated both local and systemic effects. Mucoadhesive polymeric systems can be utilized to prevent dose loss due to the mucous barriers and the formation of wet cavities. This study employed various techniques to evaluate the performance and characteristics of a mucoadhesive film composed of HPMC-PEG 400 containing retinyl palmitate and ketorolac molecules. Scanning Electron Microscopy (SEM) was employed to analyze the porous structure of the film. Thermogravimetric Analysis (TGA) was conducted at different temperatures to assess thermal stability. Fourier Transform Infrared Spectroscopy (FTIR) was used to analyze the functional groups and intermolecular interactions between the film and the drug. Swelling and weight loss tests indicated that the film disintegrated within 3–4 days. UV-VIS spectroscopy was used for drug release evaluation based on the Higuchi equation. Additionally, the surface wetting properties were assessed through contact angle measurements. The system's biocompatibility was confirmed using the MTT assay. Finally, adhesion and glide tests demonstrated the film's interaction with porcine uterine tissue. This study shows that the HPMC-PEG 400 film containing retinyl palmitate molecules interacts effectively with tissue and could be considered a novel tool for treating damaged epithelial tissues. [ABSTRACT FROM AUTHOR]

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice. Our results revealed that the absence of leptin increased lipid storage in the liver and induced significant mitochondrial alterations, which were ultimately responsible for defective ATP production and reactive oxygen species overproduction. Moreover, leptin deficiency promoted mitochondrial biogenesis, fusion, and outer membrane permeabilization. Melatonin treatment reduced the bioenergetic deficit found in ob/ob mice, alleviating some mitochondrial alterations in the electron transport chain machinery, biogenesis, dynamics, respiration, ATP production, and mitochondrial outer membrane permeabilization. Given the role of melatonin in maintaining mitochondrial homeostasis, it could be used as a therapeutic agent against adipogenic steatosis. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the main endocrine disorder in women of reproductive age worldwide. This condition is often associated with various metabolic alterations that contribute to the development of metabolic syndrome (MetS). Recent research suggests that branched-chain amino acid (BCAA) dysregulation is observed in PCOS. This study aims to investigate the relationship between dietary patterns, body composition, metabolic analytes, and serum amino acid levels in Mexican women with PCOS. Utilizing a cross-sectional design, we found that both study groups, PCOS (n = 24) and PCOS + MetS (n = 21), exhibited increased relative fat mass and dietary habits characterized by high simple sugar intake and low protein consumption, correlating with levels of relative fat mass and leptin. Notably, serum concentrations of BCAAs and glutamic acid were significantly elevated in the PCOS + MetS group. Our findings suggest that a metabolic approach may enhance the prediction and management of MetS in women with PCOS, highlighting the importance of dietary interventions in this population. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. This study investigates the therapeutic potential of secretome derived from adipose tissue mesenchymal stem cells (ASCs) in mitigating inflammation and promoting cartilage repair in an in vitro model of OA. Our in vitro model comprised chondrocytes inflamed with TNF. To assess the therapeutic potential of secretome, inflamed chondrocytes were treated with it and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and extracellular matrix markers were measured. In addition, secretome-treated chondrocytes were subject to a microarray analysis to determine which genes were upregulated and which were downregulated. Treating TNF-inflamed chondrocytes with secretome in vitro inhibits the NF-κB pathway, thereby mediating anti-inflammatory and anti-catabolic effects. Additional protective effects of secretome on cartilage are revealed in the inhibition of hypertrophy markers such as RUNX2 and COL10A1, increased production of COL2A1 and ACAN and upregulation of SOX9. These findings suggest that ASC-derived secretome can effectively reduce inflammation, promote cartilage repair, and maintain chondrocyte phenotype. This study highlights the potential of ASC-derived secretome as a novel, non-cell-based therapeutic approach for OA, offering a promising alternative to current treatments by targeting inflammation and cartilage repair mechanisms. [ABSTRACT FROM AUTHOR]

Antidepressant response is a multifactorial process related to biological and environmental factors, where brain-derived neurotrophic factor (BDNF) may play an important role in modulating depressive and anxious symptoms. We aimed to analyze how BDNF impacts antidepressant response, considering the levels of anxiety. Methods: A total of 40 depressed adults were included. We evaluated initial serum BDNF, anxiety through the State–Trait Anxiety Inventory (STAI), and the severity of depressive symptoms by the Hamilton Depression Rating Scale (HDRS). Participants received antidepressant treatment for 8 weeks, and response to treatment was evaluated according to the final HDRS scores. Results: Basal BDNF was higher in responders compared to non-responder depressed patients, in addition to being inversely associated with the severity of anxiety and depression. Conclusions: Baseline BDNF serum is an adequate predictive factor for response to antidepressant treatment with SSRI, with lower pre-treatment levels of BDNF associated with higher anxiety symptoms after treatment. Stress levels could influence the response to treatment, but its association was not conclusive. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB) remains a significant public health concern, and prediction is an important objective, particularly in the early stages of pregnancy. Many studies have relied on cervical characteristics in the mid-trimester, with limited results. It is therefore crucial to identify novel biomarkers to enhance the ability to identify women at risk. The complement pathway is implicated in the process of placentation, and recent proteomics studies have highlighted the potential roles of some complement proteins in the pathophysiology of PTB. To determine the association between the occurrence of spontaneous preterm birth (sPTB) and the concentration of complement C3, factor B, and factor H in the blood of pregnant women during the first trimester. This prospective cohort study included women with singleton pregnancies, both with and without a history of sPTB, from two health institutions in Bucaramanga, Colombia. The outcome was sPTB before 37 weeks. A blood sample was obtained between 11 + 0 to 13 + 6 weeks. ELISA immunoassay was performed to quantify the levels of C3, factor B, and factor H. A total of 355 patients were analyzed, with a rate of sPTB of 7.6% (27/355). The median plasma concentration for C3, factor B, and factor H were 488.3 μg/mL, 352.6 μg/mL, and 413.2 μg/mL, respectively. The median concentration of factor H was found to be significantly lower in patients who delivered preterm compared to patients who delivered at term (382 μg/mL vs. 415 μg/mL; p = 0.034). This study identified a significant association between low first-trimester levels of factor H and sPTB before 37 weeks. These results provide relevant information about a new possible early biomarker for sPTB. However, the results must be confirmed in different settings, and the predictive value must be examined [ABSTRACT FROM AUTHOR]

In a previous study performed by our group, pregnant women with Gestational Diabetes (GDM) showed higher vitamin D (VitD) levels in the last trimester, particularly in those requiring insulin. This phenomenon was not linked to factors like season or supplementation. This study aimed to investigate if insulin treatment in GDM affects DNA methylation in VitD metabolism genes. Thirty-two pregnant women were selected, half of whom had GDM, and were divided into insulin-treated and lifestyle groups. The DNA methylation levels in CpGs from 47 VitD metabolism-related genes were analyzed at the diagnostic visit (24–28 weeks) and before delivery. At week 36–38 of pregnancy, twenty-six CpG sites were differentially methylated (DMPs) in the insulin-treated group compared with the control group and the lifestyle group. Twenty-two of these DMPs were not different at the diagnostic visit. Six CpGs (cg18276810 (CTNNB1), cg03919554 (FGFR3), cg03984919 (NCOA1), cg19218509 (ASIP), cg09922639 (SMAD3), and cg25356935 (PDZD3)) showed significant correlations with VitD levels, not only before childbirth, but also in the postpartum period and at one year later. This suggests that insulin treatment in GDM could influence DNA methylation in genes involved in vitamin D metabolism, affecting VitD levels during and after pregnancy. Further research is warranted to elucidate these findings' clinical implications. [ABSTRACT FROM AUTHOR]

Oval cells (OCs) is the name of hepatic progenitor cells (HPCs) in rodents. They are a small population of cells in the liver with the remarkable ability to proliferate and regenerate hepatocytes and cholangiocytes in response to acute liver damage. Isolating OCs generally requires a pretreatment with special diets, chemicals, and/or surgery to induce hepatic damage and OC proliferation in mice. Unfortunately, these pretreatments are not only painful for the mice but also increase the cost of the assays, and the effects on the different organs as well as on various liver cells are still unclear. Therefore, the search for a protocol to obtain OCs without prior liver damage is mandatory. In our study, we present a protocol to isolate murine OCs from healthy liver (HL-OCs) and compare them with OCs isolated from mice pretreated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC-OCs). Our results demonstrated that cells derived from untreated mice exhibited similar behavior to those from treated mice in terms of surface marker expression, proliferation, and differentiation capacity. Therefore, given the impracticability of isolating human cells with prior hepatotoxic treatment, our model holds promise for enabling the isolation of progenitor cells from human tissue in the future. This advancement could prove invaluable for translational medicine in the understanding and treatment of liver diseases. [ABSTRACT FROM AUTHOR]

The relationships between plants and bacteria are essential in agroecosystems and bioinoculant development. The leaf endophytic Pseudomonas protegens E1BL2 was previously isolated from giant Jala maize, which is a native Zea mays landrace of Nayarit, Mexico. Using different Mexican maize landraces, this work evaluated the strain's plant growth promotion and biocontrol against eight phytopathogenic fungi in vitro and greenhouse conditions. Also, a plant field trial was conducted on irrigated fields using the hybrid maize Supremo. The grain productivity in this assay increased compared with the control treatment. The genome analysis of P. protegens E1BL2 showed putative genes involved in metabolite synthesis that facilitated its beneficial roles in plant health and environmental adaptation (bdhA, acoR, trpE, speE, potA); siderophores (ptaA, pchC); and extracellular enzymes relevant for PGPB mechanisms (cel3, chi14), protection against oxidative stress (hscA, htpG), nitrogen metabolism (nirD, nit1, hmpA), inductors of plant-induced systemic resistance (ISR) (flaA, flaG, rffA, rfaP), fungal biocontrol (phlD, prtD, prnD, hcnA-1), pest control (vgrG-1, higB-2, aprE, pslA, ppkA), and the establishment of plant-bacteria symbiosis (pgaA, pgaB, pgaC, exbD). Our findings suggest that P. protegens E1BL2 significantly promotes maize growth and offers biocontrol benefits, which highlights its potential as a bioinoculant. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called "post-acute COVID-19 syndrome" (PACS) or "long COVID-19". Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7–19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS. [ABSTRACT FROM AUTHOR]

The incidence of obesity has markedly increased globally over the last several decades and is believed to be associated with the easier availability of energy-dense foods, including high-fat foods. The reinforcing hedonic properties of high-fat foods, including olfactory cues, activate reward centers in the brain, motivating eating behavior. Thus, there is a growing interest in the understanding of the genetic changes that occur in the brain that are associated with obesity and eating behavior. This growing interest has paralleled advances in genomic methods that enable transcriptomic-wide analyses. Here, we examined the transcriptomic-level differences in the olfactory bulb and striatum, regions of the brain associated with olfaction and hedonic food-seeking, respectively, in high-fat-diet (HFD)-fed obese mice. To isolate the dietary effects from obesity, we also examined transcriptomic changes in normal-chow-fed and limited-HFD-fed groups, with the latter being pair-fed with an HFD isocaloric to the consumption of the normal-chow-fed mice. Using RNA sequencing, we identified 274 differentially expressed genes (DEGs) in the striatum and 11 in the olfactory bulb of ad libitum HFD-fed mice compared to the chow-fed group, and thirty-eight DEGs in the striatum between the ad libitum HFD and limited-HFD-fed groups. The DEGs in both tissues were associated with inflammation and immune-related pathways, including oxidative stress and immune function, and with mitochondrial dysfunction and reward pathways in the striatum. These results shed light on potential obesity-associated genes in these regions of the brain. [ABSTRACT FROM AUTHOR]

Piezo proteins have been identified as mechanosensitive ion channels involved in mechanotransduction. Several ion channel dysfunctions may be associated with diseases (including deafness and pain); thus, studying them is critical to understand their role in mechanosensitive disorders and to establish new therapeutic strategies. The current study investigated for the first time the expression patterns of Piezo proteins in zebrafish octavolateralis mechanosensory organs. Piezo 1 and 2 were immunoreactive in the sensory epithelia of the lateral line system and the inner ear. Piezo 1 (28.7 ± 1.55 cells) and Piezo 2 (28.8 ± 3.31 cells) immunopositive neuromast cells were identified based on their ultrastructural features, and their overlapping immunoreactivity to the s100p specific marker (28.6 ± 1.62 cells), as sensory cells. These findings are in favor of Piezo proteins' potential role in sensory cell activation, while their expression on mantle cells reflects their implication in the maintenance and regeneration of the neuromast during cell turnover. In the inner ear, Piezo proteins' colocalization with BDNF introduces their potential implication in neuronal plasticity and regenerative events, typical of zebrafish mechanosensory epithelia. Assessing these proteins in zebrafish could open up new scenarios for the roles of these important ionic membrane channels, for example in treating impairments of sensory systems. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) can be complicated by pulmonary arterial hypertension (PAH). Cardiopulmonary bypass (CPB) for corrective surgery may cause endothelial dysfunction, involving endothelin-1 (ET-1), circulating endothelial cells (CECs), and endothelial progenitor cells (EPCs). These markers can gauge disease severity, but their levels in children's peripheral blood still lack consensus for prognostic value. The aim of our study was to investigate changes in ET-1, cytokines, and the absolute numbers (Ɲ) of CECs and EPCs in children 24 h before and 48 h after CPB surgery to identify high-risk patients of complications. A cohort of 56 children was included: 41 cases with CHD-PAH (22 with high pulmonary flow and 19 with low pulmonary flow) and 15 control cases. We observed that Ɲ-CECs increased in both CHD groups and that Ɲ-EPCs decreased in the immediate post-surgical period, and there was a strong negative correlation between ET-1 and CEC before surgery, along with significant changes in ET-1, IL8, IL6, and CEC levels. Our findings support the understanding of endothelial cell precursors' role in endogenous repair and contribute to knowledge about endothelial dysfunction in CHD. [ABSTRACT FROM AUTHOR]

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests. [ABSTRACT FROM AUTHOR]

The ion channels Piezo 1 and Piezo 2 have been identified as membrane mechano-proteins. Studying mechanosensitive channels in chemosensory organs could help in understanding the mechanisms by which these channels operate, offering new therapeutic targets for various disorders. This study investigates the expression patterns of Piezo proteins in zebrafish chemosensory organs. For the first time, Piezo protein expression in adult zebrafish chemosensory organs is reported. In the olfactory epithelium, Piezo 1 immunolabels kappe neurons, microvillous cells, and crypt neurons, while Calretinin is expressed in ciliated sensory cells. The lack of overlap between Piezo 1 and Calretinin confirms Piezo 1's specificity for kappe neurons, microvillous cells, and crypt neurons. Piezo 2 shows intense immunoreactivity in kappe neurons, one-ciliated sensory cells, and multi-ciliated sensory cells, with overlapping Calretinin expression, indicating its olfactory neuron nature. In taste buds, Piezo 1 immunolabels Merkel-like cells at the bases of cutaneous and pharyngeal taste buds and the light and dark cells of cutaneous and oral taste buds. It also marks the dark cells of pharyngeal taste buds and support cells in oral taste buds. Piezo 2 is found in the light and dark cells of cutaneous and oral taste buds and isolated chemosensory cells. These findings provide new insights into the distribution of Piezo channels in zebrafish chemosensory organs, enhancing our understanding of their sensory processing and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

A novel MADS-box transcription factor from Pinus radiata D. Don was characterized. PrMADS11 encodes a protein of 165 amino acids for a MADS-box transcription factor belonging to group II, related to the MIKC protein structure. PrMADS11 was differentially expressed in the stems of pine trees in response to 45° inclination at early times (1 h). Arabidopsis thaliana was stably transformed with a 35S::PrMADS11 construct in an effort to identify the putative targets of PrMADS11. A massive transcriptome analysis revealed 947 differentially expressed genes: 498 genes were up-regulated, and 449 genes were down-regulated due to the over-expression of PrMADS11. The gene ontology analysis highlighted a cell wall remodeling function among the differentially expressed genes, suggesting the active participation of cell wall modification required during the response to vertical stem loss. In addition, the phenylpropanoid pathway was also indicated as a PrMADS11 target, displaying a marked increment in the expression of the genes driven to the biosynthesis of monolignols. The EMSA assays confirmed that PrMADS11 interacts with CArG-box sequences. This TF modulates the gene expression of several molecular pathways, including other TFs, as well as the genes involved in cell wall remodeling. The increment in the lignin content and the genes involved in cell wall dynamics could be an indication of the key role of PrMADS11 in the response to trunk inclination. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by a slow progression and varied symptoms. It is the second most common neurodegenerative disease, affecting over six million people in the world. Its multifactorial etiology includes environmental, genomic, and epigenetic factors. Clinical symptoms consist of non-motor and motor symptoms, with motor symptoms being the classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, and surgical interventions. Traditional pharmacological treatment consists of administering drugs (MAOIs, DA, and levodopa), while emerging evidence explores the potential of antidiabetic agents for neuroprotection and gene therapy for attenuating parkinsonian symptoms. Non-pharmacological treatments, such as exercise, a calcium-rich diet, and adequate vitamin D supplementation, aim to slow disease progression and prevent complications. For those patients who have medically induced side effects and/or refractory symptoms, surgery is a therapeutic option. Deep brain stimulation is the primary surgical option, associated with motor symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy and a portable infusion pump succeeded in reducing "off" time, where non-motor and motor symptoms occur, and increasing "on" time. This article aims to address the general aspects of PD and to provide a comparative comprehensive review of the conventional and the latest therapeutic advancements and emerging treatments for PD. Nevertheless, further studies are required to optimize treatment and provide suitable alternatives. [ABSTRACT FROM AUTHOR]

Krause's corpuscles are typical of cutaneous mucous epithelia, like the lip vermillion or the glans clitoridis, and are associated with rapidly adapting low-threshold mechanoreceptors involved in gentle touch or vibration. PIEZO1 and PIEZO2 are transmembrane mechano-gated proteins that form a part of the cationic ion channels required for mechanosensitivity in mammalian cells. They are involved in somatosensitivity, especially in the different qualities of touch, but also in pain and proprioception. In the present study, immunohistochemistry and immunofluorescence were used to analyze the occurrence and cellular location of PIEZO1 and PIEZO2 in human clitoral Krause's corpuscles. Both PIEZO1 and PIEZO2 were detected in Krause's corpuscles in both the axon and the terminal glial cells. The presence of PIEZOs in the terminal glial cells of Kraus's corpuscles is reported here for the first time. Based on the distribution of PIEZO1 and PIEZO2, it may be assumed they could be involved in mechanical stimuli, sexual behavior, and sexual pleasure. [ABSTRACT FROM AUTHOR]

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists' diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The development of specific antiviral therapies targeting SARS-CoV-2 remains fundamental because of the continued high incidence of COVID-19 and limited accessibility to antivirals in some countries. In this context, dark chemical matter (DCM), a set of drug-like compounds with outstanding selectivity profiles that have never shown bioactivity despite being extensively assayed, appears to be an excellent starting point for drug development. Accordingly, in this study, we performed a high-throughput screening to identify inhibitors of the SARS-CoV-2 main protease (Mpro) using DCM compounds as ligands. Multiple receptors and two different docking scoring functions were employed to identify the best molecular docking poses. The selected structures were subjected to extensive conventional and Gaussian accelerated molecular dynamics. From the results, four compounds with the best molecular behavior and binding energy were selected for experimental testing, one of which presented inhibitory activity with a Ki value of 48 ± 5 μM. Through virtual screening, we identified a significant starting point for drug development, shedding new light on DCM compounds. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents. [ABSTRACT FROM AUTHOR]