Tissue Sensitivity Research Articles

Metabolic and Nutritional Responses of Contrasting Aluminium-Tolerant Banana Genotypes Under Al Stress

Aluminum (Al) toxicity is a major constraint to crop productivity in acidic soils, frequently encountered in banana-growing regions. This study investigates physiological and biochemical responses to Al stress in two Cavendish banana genotypes, Baodao and Baxi (Musa acuminata L.), which exhibit contrasting levels of Al tolerance. Banana plantlets were grown hydroponically under three AlCl3 concentrations (0, 100, and 500 μM) for 24, 48, and 72 h. Root elongation was progressively inhibited with increasing Al concentrations, with Baodao showing greater inhibition than Baxi. Al primarily accumulated in roots and displayed genotype-specific distribution patterns: Baodao concentrated more Al in root tips, suggesting lower exclusion efficiency. In contrast, Baxi, the Al-tolerant genotype, translocated Al from roots to shoots more effectively, indicating potential sequestration mechanisms in less sensitive tissues. Al stress influenced enzyme activities, with Baxi exhibiting higher phosphoenolpyruvate carboxylase and citrate synthase activities at 100 µM Al, while both genotypes showed similar reductions at 500 µM. Baodao experienced more pronounced reductions in H+-ATPase activity. At 100 µM Al, Baxi retained higher levels of key nutrients (P, Zn, Mg, Mn, Fe, K, and B) in essential tissues than Baodao. However, nutrient levels were reduced in both genotypes at 500 µM Al. These findings highlight Baxi’s superior resilience under Al stress, making it a suitable genotype for cultivation and breeding in acidic soils.

The interplay between RNA m6A modification and radiation biology of cancerous and non-cancerous tissues: a narrative review.

The diverse radiation types in medical treatments and the natural environment elicit complex biological effects on both cancerous and non-cancerous tissues. Radiation therapy (RT) induces oncological responses, from molecular to phenotypic alterations, while simultaneously exerting toxic effects on healthy tissue. N6-methyladenosine (m6A), a prevalent modification on coding and non-coding RNAs, is a key epigenetic mark established by a set of evolutionarily conserved enzymes. The interplay between m6A modification and radiobiology of cancerous and non-cancerous tissues merits in-depth investigation. This review summarizes the roles of m6A in the biological effects induced by ionizing radiation and ultraviolet (UV) radiation. It begins with an overview of m6A modification and its detection methods, followed by a detailed examination of how m6A dynamically regulates the sensitivity of cancerous tissues to RT, the injury response in non-cancerous tissues, and the toxicological effects of UV exposure. Notably, this review underscores the importance of novel regulatory mechanisms of m6A and their potential clinical applications in identifying epigenetically modulated radiation-associated biomarkers for cancer therapy and estimation of radiation dosages. In conclusion, enzyme-mediated m6A-modification triggers alterations in target gene expression by affecting the metabolism of the modified RNAs, thus modulating progression and radiosensitivity in cancerous tissues, as well as radiation effects on normal tissues. Several promising avenues for future research are further discussed. This review highlights the importance of m6A modification in the context of radiation biology. Targeting epi-transcriptomic molecules might potentially provide a novel strategy for enhancing the radiosensitivity of cancerous tissues and mitigating radiation-induced injury to normal tissues.

Risk Factors and the Treatment of Type 2 Diabetes (T2D)

With the change in lifestyles, the incidence of diabetes is on the increase year by year, seriously affecting the quality of peoples lives. Among all the types of diabetes, type 2 diabetes (T2D) is the most common. The risk of T2D increases with age and the proportion of risk trends now towards youthfulness. T2D has a complex mechanism of etiology. It is generally accepted that this is a metabolic disorder mainly due to defective insulin secretion by pancreatic -cells, reduced responsiveness, and sensitivity of insulin-sensitive organs or tissues (liver, skeletal muscle, adipose tissue, etc.) to insulin. This article will summarize the associated risk factors of T2D, inform clinical practice work, and public health policy designation. Additionally, traditional antihyperglycemic drugs may lead to adverse reactions such as hypoglycemia and gastrointestinal reactions. To better control blood sugar, reduce the occurrence of adverse reactions, and delay or mitigate T2D complications, this article also lays out part of the new target drugs with therapeutic potential on the market, producing more drug selection to treat T2D. More studies targeting patients with all types of T2D are needed to better serve patients

Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients

BackgroundUp to 23% of breast cancer patients recurred within a decade after trastuzumab treatment. Conversely, one trial found that patients with low HER2 expression and metastatic breast cancer had a positive response to trastuzumab-deruxtecan (T-Dxd). This indicates that relying solely on HER2 as a single diagnostic marker to predict the efficacy of anti-HER2 drugs is insufficient. This study highlights the interaction between histamine N-methyltransferase (HNMT) and HER2 as an adjunct predictor for trastuzumab response. Furthermore, modulation of HER2 expression by HNMT may explain why those with low HER2 expression still respond to T-Dxd.MethodsWe investigated the impact of HNMT protein expression on the efficacy of anti-HER2 therapy in both in vivo and ex vivo models of patient-derived xenografts and cell line-derived xenografts. Our analysis included Förster resonance energy transfer (FRET) to assess the interaction strength between HNMT and HER2 proteins in trastuzumab-resistant and sensitive tumor tissues. Additionally, we used fluorescence lifetime imaging microscopy (FLIM), cleaved luciferase, and immunoprecipitation to study the interaction dynamics of HNMT and HER2. Furthermore, we evaluated the influence of HNMT activity on the binding of anti-HER2 antibodies to their targets through flow cytometry. We also observed the nuclear translocation of HNMT/HER2-ICD cells using fluorescent double staining and DeltaVision microscopy. Finally, ChIP sequencing was employed to identify target genes affected by the HNMT/HER2-ICD complex.ResultsThis study highlights HNMT as a potential auxiliary biomarker for diagnosing HER2 + breast cancer. FRET analysis demonstrated a significant interaction between HNMT and HER2 protein in trastuzumab-sensitive tumor tissue (n = 50), suggesting the potential of HNMT as a predictor of treatment response. Mechanistic studies revealed that the interaction between HNMT and HER2 contributes to increased HER2 protein expression at the transcriptional level, thereby impacting the efficacy of anti-HER2 therapy. Furthermore, a subset of triple-negative breast cancers characterized by HNMT overexpression was found to be sensitive to HER2 antibody–drug conjugates such as T-Dxd.ConclusionsThese findings offer crucial insights for clinicians evaluating candidates for anti-HER2 therapy, especially for HER2-low breast cancer patients who could gain from T-Dxd treatment. Identifying HNMT expression could help clinicians pinpoint patients who would benefit from anti-HER2 therapy.

Comparative evaluation of ACetic - MEthanol high salt dissociation approach for single-cell transcriptomics of frozen human tissues.

Current dissociation methods for solid tissues in scRNA-seq studies do not guarantee intact single-cell isolation, especially for sensitive and complex human endocrine tissues. Most studies rely on enzymatic dissociation of fresh samples or nuclei isolation from frozen samples. Dissociating whole intact cells from fresh-frozen samples, commonly collected by biobanks, remains a challenge. Here, we utilized the acetic-methanol dissociation approach (ACME) to capture transcriptional profiles of individual cells from fresh-frozen tissue samples. This method combines acetic acid-based dissociation and methanol-based fixation. In our study, we optimized this approach for human endocrine tissue samples for the first time. We incorporated a high-salt washing buffer instead of the standard PBS to stabilize RNA and prevent RNases reactivation during rehydration. We have designated this optimized protocol as ACME HS (ACetic acid-MEthanol High Salt). This technique aims to preserve cell morphology and RNA integrity, minimizing transcriptome changes and providing a more accurate representation of mature mRNA. We compared the ability of enzymatic, ACME HS, and nuclei isolation methods to preserve major cell types, gene expression, and standard quality parameters across 41 tissue samples. Our results demonstrated that ACME HS effectively dissociates and fixes cells, preserving cell morphology and high RNA integrity. This makes ACME HS a valuable alternative for scRNA-seq protocols involving challenging tissues where obtaining a live cell suspension is difficult or disruptive.

Slide-Ring Structured Stress-Electric Coupling Hydrogel Microspheres for Low-Loss Transduction Between Tissues.

High transductive loss at tissue injury sites impedes repair. The high dissipation characteristics in the electromechanical conversion of piezoelectric biomaterials pose a challenge. Therefore, supramolecular engineering and microfluidic technology is utilized to introduce slide-ring polyrotaxane and conductive polypyrrole to construct stress-electric coupling hydrogel microspheres. The molecular slippage mechanism of slide-ring structure stores and releases mechanical energy, reducing mechanical loss, the piezoelectric barium titanate enables stress-electricity conversion, and conjugated π-electron movement in conductive network improves the internal electron transfer efficiency of microspheres, thereby reducing the loss in stress-electricity conversion for the first time. Compared to traditional piezoelectric hydrogel microspheres, the stress-electric coupling efficiency of low-dissipation microspheres increased by 2.3 times, and the energy dissipation decreased to 43%. At cellular level, electrical signals generated by the microspheres triggered Ca2+ influx into stem cells and upregulated the cAMP signaling pathways, promoting chondrogenic differentiation. Enhanced electrical signals induced macrophage polarization to the M2 phenotype, reshaping inflammation and promoting tissue repair. In vivo, the low-dissipation microspheres restored low-loss transduction between tissues, alleviated cartilage damage, improved behavioral outcomes, and promoted the treatment of osteoarthritis in rats. Therefore, this study proposes a new strategy for restoring low-loss transduction between tissues, particularly in mechanically sensitive tissues.

Mechanistic studies of PFKFB2 reveals a novel inhibitor of its kinase activity.

The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) family of proteins are bifunctional enzymes that are of clinical relevance because of their roles in regulating glycolysis in insulin sensitive tissues and cancer. Here, we sought to express recombinant PFKFB2 and develop a robust protocol to measure its kinase activity. These studies resulted in the unexpected finding that bacterially expressed PFKFB2 is phosphorylated in situ on Ser483 but is not a result of autophosphorylation. Recombinant PFKFB2 was used to develop an enzymatic assay to test a library of molecules selected by the Atomwise AtomNet® AI platform. This resulted in the identification of a new inhibitor, B2, that inhibits PFKFB2 (IC50 3.29 μM) and PFKFB3 (IC50 11.89 μM). A-498 cells, which express both PFKFB2 and PFKFB3, were treated with B2. Seahorse XFe analysis revealed B2 inhibited cellular glycolysis and glycolytic capacity. Targeted LC/MS analysis showed B2 decreased fructose-1,6-bisphosphate and downstream glycolytic intermediates but increased fructose-6-phosphate levels, which is consistent with an inhibitory effect on PFK-1 activity. The LC/MS metabolic profile of A-498 cells treated under identical conditions with the known PFKFB3 inhibitor, PFK158, was distinct from that induced by B2. These results thus demonstrate the identification and validation of a new PFKFB kinase inhibitor.

Prospects for the use of a combined agent with prebiotic action to improve the effectiveness of type 2 diabetes therapy

Type 2 diabetes mellitus is a chronic disease characterized by impaired insulin secretion in the body and loss of tissue sensitivity to it. Treatment of the disease is still not effective enough, which is due to the multifactorial nature of the development of carbohydrate metabolism disorders, the mechanisms of which have not yet been fully elucidated. Also, the complexity of its treatment is associated with the occurrence of side effects when taking first-line drugs. Among the most important complications is a decrease in the concentration of several groups of vitamins that play a key role in maintaining the health of the body and metabolic processes, including participation in the regulation of blood glucose levels. Studies show that a deficiency of vitamins D, B12, C and some others can increase the risk of developing diabetes progression. Therefore, it is important to maintain a balance of vitamins in the body through proper nutrition or taking vitamin complexes, such as Mezi-Vit Plus.

Development of a sterilization process for amniotic membrane allograft tissue using supercritical carbon dioxide and NovaKill

Amniotic membrane is arguably one of the most popular biological wound dressings on the market today. Various growth factors and cytokines inherent to amniotic membrane tissue have been recognized as key mediators in wound healing and tissue regeneration, giving the tissue its clinical utility. Sterilization methodologies using irradiation are recognized as the gold standard in the field and routinely used to prepare tissue allografts, including amniotic membrane for transplantation. However, irradiation is not always compatible in preserving the physical structure or biochemical factors of biological materials and can potentially result in detrimental effects to the critical quality attributes of allograft tissues. Alternatively, a novel sterilization technique involving supercritical carbon dioxide (SCCO2) has been shown to have minimal effect on the inherent biophysical properties of sensitive biological tissues and tissue-derived products. At BioBridge Global, we have developed a process utilizing SCCO2 technology for the sterilization of an amniotic membrane tissue allograft product. This process, first and foremost, meets industry standards for sterilization while simultaneously maintaining the biochemical composition of the tissue. Our results show that upon SCCO2 sterilization, most of the growth factors tested were conserved, with many at quantities significantly greater than commercially available gamma and electron beam irradiated tissue. The SCCO2-sterilized amniotic membrane allograft is unique in that it is designed to overcome limitations associated with traditional tissue sterilization methodologies, namely, the conservation of key biological factors inherent to native amniotic membrane tissue. It is anticipated that by retaining these biological factors, clinical outcomes associated with the use of SCCO2-sterilized amniotic membrane will be improved.

Current opportunities for the prevention and treatment of carbohydrate metabolism disorders

Diabetes mellitus poses a significant threat to the health and lives of people worldwide. Consequently, the timely identification of individuals at risk and the prevention of disease development are of utmost importance. Increasing physical activity, reducing body weight, and quitting smoking are effective measures for preventing type 2 diabetes. When lifestyle modifications are insufficient, pharmacological glucose-lowering therapy is prescribed. The endocrinologist’s arsenal is dominated by drugs that have a predominant effect on hyperglycemia. Metformin is the 1st line of therapy for disorders of carbohydrate metabolism. It is known that insulin resistance is the main cause of the development and progression of complications of diabetes mellitus. Correction of insulin resistance looks like a promising drug tactic. However, the choice of a drug for these purposes is currently limited. Currently, new, promising drugs are being developed that can increase tissue sensitivity to insulin. Subetta is an original insulin sensitizer that helps to enhance insulin-dependent glucose metabolism. This is a complex drug that increases the sensitivity of tissues to insulin, and normalizes the function of the vascular endothelium, as well as helps to increase the level of adiponectin. A decrease in glycemic parameters, a reduction of the insulin resistance index (HOMA-index) and weight stabilization has been shown in the clinical studies. All-Russian observational non-interventional study is planned to assess the effectiveness of Subetta in real-world clinical practice for patients with prediabetes or type 2 diabetes (SILA). The study includes data from 2,500 patients approximately over the age of 18. The findings of this programme enable a comprehensive evaluation of the effectiveness of combined glucose-lowering therapy in conjunction with Subetta, based on the dynamic assessment of both clinical and laboratory parameters, as well as quality of life questionnaires.

Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin.

Clarification of cisplatin resistance may provide new targets for therapy in cisplatin resistant ovarian cancer. The current study aims to explore involvement of isoforms of AU-rich element RNA-binding protein 1 (AUF1) in cisplatin resistance in ovarian cancer. The cancer stem cell-like features were analyzed using colony formation assay, tumor sphere formation assay and nude mouse xenograft experiments. AUF1 isoforms expression was analyzed using immunoblotting, qRT-PCR, and immunohistochemistry. RIP and Biotin pulldown was used to analyze the interaction of SRSF2 and hnRNPA1 with AUF1 transcript. Transcriptome regulated by AUF1 isoforms was analyzed by RNA-seq. The current study demonstrated differential expression of AUF1 isoforms in cisplatin sensitive and resistant ovarian cancer tissues and cells. P37 isoform promoted proliferation, while p45 isoform enhanced responsiveness of ovarian cancer cells to cisplatin. the clonal formation capacity of the cells, and the restoration of p45 expression reduced the capacity with cisplatin treatment. The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc-modified SRSF2 on AUF1 exon 2 and exon 7 regulated the alternative splicing of AUF1. The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc modified SRSF2 on exon 2 and exon 7 regulated the alternative splicing of AUF1 and subsequent isoform expression. P37 isoform played a "cancer promoter" role, p42 and p45, especially p45 played a "cancer suppressor" role in ovarian cancer. This study provides a new target for exploring the drug resistance mechanism of ovarian cancer.

Comparative Analysis of Silicone Mouth Swabs with Varying Hardness Levels for Optimal Plaque Removal in Elderly Oral Care.

Silicone mouth swabs have emerged as a promising alternative to gauze, sponge brushes, and soft-bristled toothbrushes, offering a balance between gentle cleaning and effectiveness. The flexibility and softness of silicone make it a suitable material for safely cleaning the sensitive oral tissues of elderly patients. This study aims to determine the optimal hardness level of silicone that maximises cleaning effectiveness while minimising the risk of trauma to oral tissues. A pseudo-plaque was created by mixing 6.0 g of Thicken Up Clear food additive with 12.0 ml of water and food colouring, which was then spread onto a NISSIN dentoform silicone rubber sheet (simulated soft tissue) with a thickness of 2.0 mm. Silicone heads with different hardness levels - 20, 30, 40, 50, and 60 Shore A - were attached to a V.P.2000 tooth brushing machine, operating at 75 rounds per minute with a force of 1.96 N. Each swab was used to brush the surface 25 times (n = 16 for each group). A one-way analysis of variance (ANOVA) revealed a statistically significant difference in pseudo-plaque removal among the five hardness levels, with an F-value of 106.161 (degrees of freedom = 4, 75, p 0.001). The Games-Howell pairwise comparison test showed that all five silicone hardness levels differed significantly from each other in their effectiveness in removing pseudo-plaque (p 0.05). No visible simulated soft tissue damage was observed before and after brushing, as inspected with a stereomicroscope in all experiments. The silicone oral swab with a hardness level of 60 Shore A was found to maximise pseudo-plaque removal in vitro. This finding is crucial for the development of specialised oral hygiene tools tailored to the needs of the elderly population, thereby enhancing oral health and overall well-being.

Analysis of the Porphyrin Peak Shift and Fluorescence Lifetime in Gliomas with Different Tumor Grades, Intratumoral Regions, and Visible Fluorescence Status.

Background: 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence shows high sensitivity in detecting the tumor core of high-grade gliomas (HGG) but poor sensitivity for tissue of low-grade gliomas (LGG) and the margins of HGG. The characteristic emission peak for PpIX is known to be located at 635 nm. Recently, a second emission peak was described at 620 nm wavelength in LGG and the tumor infiltration zone of HGG. Methods: During surgery, samples from the tumor core and tumor infiltration zone of 43 WHO grade 2-4 gliomas were collected after preoperative 5-ALA administration, and their PpIX emission spectra, as well as fluorescence lifetimes, were determined by ex vivo analysis. Subsequently, the relative PpIX peak contribution (RPPC) was retrieved by calculating the integral of the two bands corresponding to the two emission peaks of PpIX (615-625 nm, 625-635 nm) and correlated with fluorescence lifetimes. Results: The mean RPPC decreased in samples with descending order of WHO grades, non-fluorescing samples, and infiltrative tumor regions, indicating a shift toward the 620 nm peak in porphyrin fluorescence. The porphyrin peak shift across all specimens correlated with lower fluorescence lifetimes (R: 0.854, R-squared: 0.729). Conclusions: The observed peak shift has important implications for fluorescence lifetime analyses since the lifetimes of other porphyrins contribute to the overall decay dynamics. Based on these initial data using fluorescence lifetime, this knowledge is of major importance, especially for detecting tissue from LGG that lack visible fluorescence, to further optimize the visualization of these tumor tissue using this promising imaging modality.

Management of Temporoparietal Flap on Difficult Facial Deformities With Minimal Donor Site Morbidity.

The aim of this study is to investigate the use of the temporoparietal fascial flap (TPFF) in the repair of tissue defects in the head and neck region. TPFF is a preferred method among surgeons due to its thin and flexible structure and its strong vascular structure supplied by the superficial temporal artery. In the study, the operations performed on a total of 21 patients and the results of these operations were analyzed. TPFF has been used in the repair of facial and neck deformities caused by various reasons such as trauma, infection, Romberg syndrome and skin tumors. It has been reported that TPFF, which can be applied as a pedicled or free flap, gives aesthetically satisfactory results without significant complications on the flap. However, minor complications such as partial flap loss, hematoma and skin graft loss were observed in four patients. These complications were resolved by surgical interventions. In conclusion, TPFF is defined as an effective and safe option for the repair of various tissue defects with minimal donor-site morbidity. Thanks to the thin and flexible structure of the flap, aesthetic harmony is achieved although the risk of complications remains at low levels. Therefore, TPFF stands out as an important option for surgeons, especially in the elimination of facial contour irregularities and repair of sensitive tissue areas.

Fast Multi-Distance Time-Domain NIRS and DCS System for Clinical Applications.

We have designed and built an improved system for combined Time-Domain Near-Infrared Spectroscopy (TD NIRS) and Diffuse Correlation Spectroscopy (DCS) measurements. The system features two independent channels, enabling TD NIRS and DCS acquisition at short and long source-detector distances to enhance depth sensitivity in layered tissues. Moreover, the device can operate at fast acquisition rates (up to 50 Hz) to monitor hemodynamic oscillations in biological tissues. An OEM (Original Equipment Manufacturer) TD NIRS device enables stable and robust acquisition of photon distribution of time-of-flight. For the DCS signals, the use of a time tagger and a software correlator allows us flexibility in post-processing. A user-friendly GUI controls TD NIRS data acquisition and online data analysis. We present results for the system characterization on calibrated tissue phantoms according to standardized protocols for performance assessment of TD NIRS and DCS devices. In-vivo measurements during rest and during vascular occlusions are also reported to validate the system in real settings.

Bioaccumulation and biochemical impact of polyethylene terephthalate microplastics in Cipangopaludina chinensis: Tissue-specific analysis and homeostasis disruption

Microplastics are a novel pollutant that adversely affect freshwater benthic organisms. However, few studies have investigated the mechanism underlying the bioaccumulation and the toxicity of microplastics. In this study, microplastics bioaccumulation of wild Cipangopaludina chinensis in the Songhua River were utilized, and a 28-day aquatic toxicity test was performed to determine the effects of exposure to polyethylene terephthalate (PET), the bioaccumulation of PET, and changes in multiple biomarkers in the muscle, gill, and kidney tissues. The concentration pattern of microplastics was as follows: kidney tissue > muscle tissue > gill tissue. Microplastic ingestion caused AChE inhibition led to significant increases in redox and energy metabolism indicators. Furthermore, the IBR analysis presented a "response-resistance-breakdown" process, indicating that Cipangopaludina chinensis possessed resistance with time (D14 and D21) and concentration (0.10 mg/L and 1.00 mg/L) thresholds. Tissue sensitivity to microplastics was ranked as gill > muscle > kidney, which was the opposite order of microplastic accumulation. These findings implied that less sensitive tissues stored a larger amount of pollutants, suggesting a reduction in tissue sensitivity to microplastics with higher microplastic occurrence rates. This study provides new insights into biological resistance to pollutant stress, warranting further investigation into the underlying mechanisms.

Premature Thelarche: An Updated Review.

Premature thelarche is the most common pubertal disorder in girls. The condition should be differentiated from central precocious puberty which may result in early epiphyseal fusion and reduced adult height, necessitating treatment. The purpose of this article is to familiarize physicians with the clinical manifestations of premature thelarche and laboratory tests that may help distinguish premature thelarche from central precocious puberty. A search was conducted in September 2022 in PubMed Clinical Queries using the key term "Premature thelarche". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used to compile the present article. Premature thelarche denotes isolated breast development before the age of 8 years in girls who do not manifest other signs of pubertal development. The condition is especially prevalent during the first two years of life. The majority of cases of premature thelarche are idiopathic. The condition may result from an unsuppressed hypothalamic-pituitary-gonadal axis in the early years of life, an "overactivation" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors controlling sexual maturation, increased circulating free estradiol, increased sensitivity of breast tissue to estrogens, and exposure to exogenous estrogens. The cardinal feature of premature thelarche is breast development which occurs without additional signs of pubertal development in girls under 8 years of age. The enlargement may involve only one breast, both breasts asymmetrically, or both breasts symmetrically. The breast size may fluctuate cyclically. The enlarged breast tissue may be transiently tender. There should be no significant changes in the nipples or areolae and no pubic or axillary hair. The vulva, labia majora, labia minora, and vagina remain prepubertal. Affected girls have a childlike body habitus and do not have mature contours. They are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development remain normal. Most cases of premature thelarche can be diagnosed on clinical grounds. Laboratory tests are seldom indicated. No single test can reliably differentiate premature thelarche from precocious puberty. Premature thelarche is benign, and no therapy is necessary apart from parental reassurance. As enlargement of breasts may be the first sign of central precocious puberty, a prolonged follow- up period every 3 to 6 months with close monitoring of other pubertal events and linear growth is indicated in all instances.

MicroRNA Analysis in Meningiomas with Different Degrees of Tissue Stiffness: A Potential Tool for Effective Preoperative Planning.

Meningioma, the most common primary intracranial tumor, presents challenges in surgical treatment because of varying tissue stiffness. This study explores the molecular background of meningioma stiffness, a critical factor in surgical planning and prognosis, focusing on the utility of microRNAs (miRNAs) as diagnostic biomarkers of tissue stiffness. Patients with meningiomas treated surgically at the University Hospital Brno were included in this study. Total RNA, isolated from tumor tissue samples, underwent quality control and small RNA sequencing to analyze miRNA expression. Differentially expressed miRNAs were identified, and their association with tumor stiffness was assessed. This study identified specific miRNAs differentially expressed in meningiomas with different stiffness levels. Key miRNAs, such as miR-31-5p and miR-34b-5p, showed significant upregulation in stiffer meningiomas. These findings were validated using reverse transcription-quantitative polymerase chain reaction, revealing a potential link between miRNA expression and tumor consistency. The expression of miR-31-5p was most notably associated with the stiffness of the tumor tissue (sensitivity = 71% and specificity = 83%). This research highlights the potential of miRNAs as biomarkers for determining meningioma tissue stiffness. Identifying specific miRNAs associated with tumor consistency could improve preoperative planning and patient prognosis. These findings pave the way for further exploration of miRNAs in the clinical assessment of meningiomas.

An optimized fractionation method reveals insulin-induced membrane surface localization of GLUT1 to increase glycolysis in LβT2 cells

Insulin is an important regulator of whole-body glucose homeostasis. In insulin sensitive tissues such as muscle and adipose, insulin induces the translocation of glucose transporter 4 (GLUT4) to the cell membrane, thereby increasing glucose uptake. However, insulin also signals in tissues that are not generally associated with glucose homeostasis. In the human reproductive endocrine axis, hyperinsulinemia suppresses the secretion of gonadotropins from gonadotrope cells of the anterior pituitary, thereby linking insulin dysregulation to suboptimal reproductive health. In the mouse, gonadotropes express the insulin receptor which has the canonical signaling response of IRS, AKT, and mTOR activation. However, the functional outcomes of insulin action on gonadotropes are unclear. Here, we demonstrate through use of an optimized cell fractionation protocol that insulin stimulation of the LβT2 gonadotropic cell line results in the unexpected translocation of GLUT1 to the plasma membrane. Using our high purity fractionation protocol, we further demonstrate that though Akt signaling in response to insulin is intact, insulin-induced translocation of GLUT1 occurs independently of Akt activation in LβT2 cells.

Promising Directions for Regulating Signaling Pathways Involved in the Type 2 Diabetes Mellitus Development

Many studies confirm that substances of natural origin have a pronounced affinity for type 2 diabetes mellitus (T2DM) therapeutic targets. At the moment, there is growing interest in bioactive peptides, phytochemicals, and drugs from other natural sources as highly effective, safe and promising antidiabetic agents. Natural sources are a promising resource for regulating several pathological pathways in T2DM. The review describes ways to mitigate insulin resistance and tissue sensitivity to glucose through PTP1β (protein tyrosine phosphatase 1β), GLP-1R (glucagon-like peptide receptor), DPP-4 (dipeptidyl peptidase-4), AMPK (adenosine monophosphate activated protein kinase), MAPK (mitogen-activated protein kinase). Regulation of obesity and oxidative stress development through CCN3 (nephroblastoma overexpressed gene), PPAR-γ (peroxisome proliferator-activated receptor γ), Nrf2 (nuclear factor erythroid-related factor 2), FFAR (free fatty acid receptors), 11β-HSD1 (11β-hydroxysteroid dehydrogenase). Regulation of hyperglycemia through alpha-amylase inhibitors, regulation of glucose metabolism through GFAT (glutamine fructose-6-phosphate aminotransferase), FOXO1 (forkhead box protein O1), GLUT4 (glucose transporter type 4), PGC-1α (receptor gamma coactivator 1α activating peroxisome proliferator). The review examines the use of natural sources, from which low-molecular-weight and peptide compounds are used as T2DM targets modulators.