Search Results (352)

Background: Peritoneal dissemination in colorectal cancer (CRC) is associated with poor prognosis due to limited efficacy of current therapeutic strategies. The cholinergic receptor nicotinic beta 2 subunit (CHRNB2), a component of the acetylcholine receptor, has been implicated in other malignancies, but its role in CRC remains unknown. Methods: This study evaluated the expression and function of CHRNB2 in CRC. CHRNB2 mRNA levels were quantified by qRT-PCR in cell lines and clinical specimens. Functional assays were conducted using CRC cell lines with high CHRNB2 expression, in which CHRNB2 was knocked down by shRNA. Cell proliferation, migration, and invasion were assessed in vitro. In vivo effects were evaluated using subcutaneous and peritoneal xenograft models. The impact of CHRNB2 monoclonal antibody (mAb) treatment on CRC cell proliferation was also examined. Clinical correlations were assessed between CHRNB2 expression and clinicopathological features, including recurrence patterns. Results: CHRNB2 expression varied among CRC cell lines, with the highest levels observed in LOVO cells. CHRNB2 knockdown significantly inhibited proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo. CHRNB2 mAb treatment reduced cell proliferation. Clinically, high CHRNB2 expression correlated with a significantly higher cumulative rate of peritoneal recurrence, but not with recurrence in the liver, lungs, or lymph nodes. Multivariate analysis identified high CHRNB2 expression and T4 tumor depth as independent predictors of peritoneal recurrence. Conclusions: CHRNB2 promotes the malignant phenotype of CRC, particularly in peritoneal dissemination. These findings suggest that CHRNB2 may serve as a novel diagnostic biomarker and therapeutic target for CRC with peritoneal metastasis. Full article

Background: Allergic rhinitis (AR) is a prevalent allergic disorder characterized by a complex pathogenesis. Drawing on traditional Chinese medicine theory and contemporary pharmacological principles, this study developed an inhalation-based herbal formulation, ZHW, to explore a novel non-invasive therapeutic approach. Objective: To investigate the therapeutic effects of ZHW on AR and elucidate its underlying mechanisms and potential targets through an integrated analysis of network pharmacology and proteomics. Materials and Methods: The volatile components of ZHW were analyzed by gas chromatography–mass spectrometry (GC-MS). The mouse model of AR was induced by OVA sensitization. The therapeutic efficacy of ZHW was assessed based on nasal symptom scores, histopathological examination, and inflammatory cytokine levels. Furthermore, the underlying mechanisms and potential targets of ZHW were investigated through integrated network pharmacology and proteomics analyses. Results: GC-MS analysis identified 39 bioactive compounds in ZHW. Inhalation treatment with ZHW demonstrated significant anti-allergic effects in OVA-sensitized mice, as evidenced by (1) reduced sneezing frequency and nasal rubbing behaviors; (2) decreased serum levels of IL-4, histamine, and OVA-specific IgE; (3) attenuated IL-4 concentrations in both nasal lavage fluid and lung tissue; (4) diminished nasal mucosal thickening; and (5) suppression of inflammatory cell infiltration. Integrated network pharmacology and proteomics analyses indicated that ZHW’s therapeutic effects were mediated through the modulation of multiple pathways, including the PI3K-Akt signaling pathway, the B cell receptor signaling pathway, oxidative phosphorylation, and the FcεRI signaling pathway. Key molecular targets involved Rac1, MAPK1, and SYK. Molecular docking simulations revealed strong binding affinities between ZHW’s primary bioactive constituents (linalool, levomenthol, linoleic acid, Linoelaidic acid, and n-Valeric acid cis-3-hexenyl ester) and these target proteins. Conclusions: The herbal formulation ZHW demonstrates significant efficacy in alleviating allergic rhinitis symptoms through multi-target modulation of key signaling pathways, including PI3K-Akt- and FcεRI-mediated inflammatory responses. These findings substantiate ZHW’s therapeutic potential as a novel, non-invasive treatment for AR and provide a strong basis for the development of new AR therapies. Future clinical development will require systematic safety evaluation to ensure optimal therapeutic outcomes. Full article

In clinical applications of surface-enhanced Raman spectroscopy (SERS) immunosensors, accurately determining analyte biomarker concentrations is essential. This study presents a non-invasive approach for quantifying various breast cancer biomarkers—including human epidermal growth factor receptor II (HER-II) (2+, 3+ (I), 3+ (II), 3+ (III), and positive IV) and CA 15-3—using a directional, plasmonically active, label-free SERS sensor. Each stage of sensor functionalization, conjugation, and biomarker interaction was verified by UV–Vis spectroscopy. Atomic force microscopy (AFM) characterized the morphology of gold nanourchin (GNU)-immobilized printed circuit board (PCB) substrates. An enhancement factor of ≈ 0.5 × 10⁵ was achieved using Rhodamine 6G as the probe molecule. Calibration curves were initially established using standard HER-II solutions at concentrations ranging from 1 to 100 ng/mL and CA 15-3 at concentrations from 10 to 100 U/mL. The SERS signal intensities in the 620–720 nm region were plotted against concentration, yielding linear sensitivity with R² values of 0.942 and 0.800 for HER-II and CA15-3, respectively. The same procedure was applied to breast cancer serum (BCS) samples, allowing unknown biomarker concentrations to be determined based on the corresponding calibration curves. SERS data were processed using the filtfilt filter from scipy.signal for smoothing and then baseline-corrected with the Improved Asymmetric Least Squares (IASLS) algorithm from the pybaselines.Whittaker library. Principal Component Analysis (PCA) effectively distinguished the sample groups and revealed spectral differences before and after biomarker interactions. Key Raman peaks were attributed to functional groups including N–H (primary and secondary amines), C–H antisymmetric stretching, C–N (amines), C=O antisymmetric stretching, NH₃⁺ (amines), carbohydrates, glycine, alanine, amides III, C=N stretches, and NH₂ in primary amides. Full article

Pathological complete response (pCR) following neoadjuvant therapy for IBC has shown a strong correlation with event-free survival and overall survival. Over the past three decades, the five-year net survival rate for breast cancer has generally increased; however, several Eastern European countries exhibit lower survival rates. Data from Romania, specifically regarding Her2-positive breast cancer response to therapy, are notably limited. Background/Objectives: The aim of our study was to evaluate the response to NAT using chemotherapy and Her2-targeted therapy in a cohort of 167 patients diagnosed with invasive breast cancer in our institution. Methods: We retrospectively analyzed 167 consecutive cases diagnosed with IBC in our institution between January 2020 and September 2024 with Stages II and III Her2-positive IBC. The overall pCR rates and several factors cited in the literature as predictors of pCR were analyzed. Results: Overall, the pCR rate was 50.29%, with higher values in 3+ cases (62.28%) compared to 2+ cases/ISH amplified (24.53%). Higher pCR rates were observed in hormone-negative cases, Stage II cases, estrogen receptor-negative cases, and high Ki-67 values. Patient age, ISH group, Her2 copy number, Her2:CEP17 ratio, and clinical lymph node involvement did not seem to influence pCR rates in our study. Conclusions: The data presented in our study represent, to the best of our knowledge, the largest cohort of patients diagnosed with Her2-positive IBC from Romania. The presented results and the pCR predictive factors were comparable to those cited in other studies on Her2-positive IBC cases. Full article

Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that helps the body regulate blood pressure and endocrine secretions. Transmembrane serine protease 2 (TMPRSS2) is a cell surface protein expressed mainly by endothelial cells of the respiratory and digestive tract, which participates in the cleavage of protein peptide bonds with serine as the active site. These two proteins have been studied to be highly associated with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soybean trypsin inhibitor (SBTI) has special bioactivities such as anticarcinogenic and anti-inflammatory functions, which can be widely used in functional foods or drugs. Our study involved in vitro and in vivo experiments to elucidate the effect of SBTI on SARS-CoV-2 host invasion. First, it was confirmed that being under 250 μg/mL of SBTI was not toxic to HepG2, HEK293T, and Calu-3 cells. The animal study administered SBTI to mice once daily for 14 days. In the lungs, liver, and kidneys, the histopathologic findings of the SBTI group were not different from those of the control group, but the expression of ACE2, TMPRSS2, and CD147 was reduced. Thus, our findings suggest that the inhibition of ACE2, TMPRSS,2 and CD147 proteins by SBTI shows promise in potentially inhibiting SARS-CoV-2 infection. Full article

Breast cancer is the leading threat to the health of women, with a rising global incidence linked to social and psychological factors. Among its subtypes, triple-negative breast cancer (TNBC), which lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is highly heterogeneous with early metastasis and a poor prognosis, making it the most challenging subtype. Mounting evidence shows that the mitochondrial quality control (MQC) system is vital for maintaining cellular homeostasis. Dysfunction of the MQC is tied to tumor cell invasiveness, metastasis, and chemoresistance. This paper comprehensively reviews the molecular link between MQC and TNBC development. We focused on how abnormal MQC affects TNBC progression by influencing chemoresistance, immune evasion, metastasis, and cancer stemness. On the basis of current studies, new TNBC treatment strategies targeting key MQC nodes have been proposed. These findings increase the understanding of TNBC pathogenesis and offer a theoretical basis for overcoming treatment challenges, providing new research angles and intervention targets for effective precision therapy for TNBC. Full article

Background: Breast cancer is the most commonly diagnosed neoplasm in women and is classified into different molecular subtypes based on the expression characteristics of estrogen and progesterone receptors (ERs and PRs) and human epidermal growth factor 2 (HER2, ERBB2): Luminal A, Luminal B, HER2(+), and triple-negative breast cancer (TNBC). Telocytes, a new type of stromal cell, provide structural support for the preservation of organ integrity and play a crucial role in the tumor microenvironment. In this study, we evaluated telocyte counts and expression profiles among breast cancer subtypes. Methods: The quantitative differences between telocytes in three subtypes of invasive breast cancer were assessed via immunohistochemistry, using vimentin, CD10, CD34, and c-Kit antibodies. Results: Vimentin(+), CD10(+), CD34(+), and c-Kit(+) telocyte counts were significantly higher in the Luminal and HER2(+) groups than in TNBC (p = 0.000 for vimentin, CD10, CD34, and c-Kit in Luminal vs. TNBC; p = 0.006 for CD34 in HER2(+) vs. TNBC). CD10(+), CD34(+), and c-Kit(+) telocyte counts were significantly higher in ER(+) than in ER(–) patients (p = 0.006, p = 0.000, and p = 0.009, respectively) and in PR(+) than in PR(–) patients (p = 0.018, p = 0.000, and p = 0.044, respectively). The presence of ER/c-Kit(+) telocytes was demonstrated, and c-Kit(+) telocyte counts were significantly lower in tumors larger than 5 cm than in those measuring 2–5 cm (p = 0.032). Conclusions: Our results showed quantitative differences and marker expression profiles for telocytes between different breast cancer molecular subtypes. c-Kit(+) telocytes may contribute to the regulation of tumor size. Full article

Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive biopsies and time-intensive laboratory procedures. In this study, we present a biosensor integrated with a reusable printed circuit board (PCB) and functionalized glucose test strips designed for rapid and non-invasive HER2 detection in saliva. The biosensor achieved a limit of detection of 10⁻¹⁵ g/mL, 4 to 5 orders of magnitude more sensitive than the enzyme-linked immunosorbent assay (ELISA), with a sensitivity of 95/dec and a response time of 1 s. In addition to HER2, the biosensor also detects cancer antigen 15-3 (CA15-3), another clinically relevant breast cancer biomarker. The CA15-3 test demonstrated an equally low limit of detection, 10⁻¹⁵ g/mL, and a higher sensitivity, 190/dec, further validated using human saliva samples. Clinical validation using 29 saliva samples confirmed our biosensor’s ability to distinguish between healthy, in situ breast cancer, and invasive breast cancer patients. The system, which integrates a Bluetooth Low-Energy (BLE) module, enables remote monitoring, reduces hospital visits, and enhances accessibility for point-of-care and mobile screening applications. This ultra-sensitive, rapid, and portable biosensor can serve as a promising alternative for breast cancer detection and monitoring, particularly in rural and underserved communities. Full article

Ductal carcinoma in situ (DCIS) is the most common form of non-invasive breast cancer and a recognized precursor to invasive ductal carcinoma (IDC). Although DCIS itself is confined to the milk duct and not immediately life-threatening, its potential for progression to invasive disease necessitates careful clinical management. The increased detection of DCIS due to advancements in imaging and widespread screening programs has raised critical questions regarding its classification, prognosis, and optimal treatment strategies. While most cases exhibit indolent behavior, others harbor molecular characteristics that drive malignant transformation. A key challenge lies in distinguishing low-risk DCIS, which may never progress, from aggressive cases requiring intervention. Tumor microenvironment dynamics, immune cell infiltration, and molecular alterations, including hormone receptor (HR) status, human epidermal growth factor 2 (HER2) expression, and genetic mutations, play crucial roles in determining disease trajectory. This review explores the biological and molecular mechanisms underlying DCIS progression, with an emphasis on myoepithelial cells, tumor-infiltrating lymphocytes, and microenvironmental factors. By integrating recent findings, this article aims to refine risk stratification approaches and guide future strategies for personalized DCIS management. Improved prognostic biomarkers and targeted therapeutic interventions could help optimize treatment decisions, balancing the need for effective cancer prevention while minimizing overtreatment in low-risk patients. Full article

Coronary artery disease and vitamin D deficiency are both widespread conditions with a high incidence worldwide. Coronary artery disease is a complex illness with variable manifestation and pathogenesis. It often involves the development of atherosclerosis, and it frequently has serious or even fatal consequences for the patient. Vitamin D receptor expression is found in many tissues throughout the body, which results in a broad effect of the vitamin. Studies have found correlations between vitamin D deficiency and the development of coronary artery disease as well as other cardiovascular diseases, such as hypertension. This review will discuss randomized controlled trials conducted from 2020 forward, aiming to elucidate whether vitamin D supplements have the potential to be used as an add-on treatment for coronary artery disease. The randomized controlled trials all used vitamin D as intervention and tested a population suffering from coronary artery disease or the risk of developing it. Even though animal studies found evidence that vitamin D can regulate inflammation, lipid profile, foam cell formation, vessel reactivity, and blood pressure, which are all mediators in the development of atherosclerosis, the results from the randomized controlled trials were ambiguous. The general older population did not seem to benefit from the treatment, but different subgroups such as patients with type 2 diabetes and patients with more developed coronary artery disease exhibited some positive effects from the treatment. Furthermore, vitamin D showed cardioprotective effects following coronary artery bypass surgery, which make it a possible add-on treatment before invasive coronary intervention. The question in focus still needs further research and a more focused approach on subgroups that may benefit from treatment. Full article

Background/Objectives: Chondrosarcoma (CS), the most common malignant bone tumor in adults, exhibits a poor prognosis due to high rates of post-surgical recurrence and metastasis, and resistance to chemotherapy. CS’s abundant expression of aspartyl-asparaginyl-β-hydroxylase (ASPH), which drives invasive tumor growth via Notch and PI3K/mTOR activation, opens opportunities for treatment in combination with standard Doxorubicin (DOX) chemotherapy. We hypothesized that the small molecule inhibitor SMI1182, which targets the catalytic domain of ASPH, and BEZ235, which targets PI3K/mTOR, could enhance the chemotherapeutic effects of DOX. Human CS1 (Grade 3) and CDS11 (Grade 2) conventional CS cell lines were treated with broad dose ranges of DOX, BEZ235, or SMI1182 as mono- or combination therapy to assess their anti-tumor effects on cell viability, toxicity, and motility. Methods: Mechanistic studies included the analysis of ASPH expression, Notch signaling, and insulin/IGF/IRS pathway activation through mTOR. DOX, BEZ235, or SMI1182 treatments caused dose-dependent cell loss and cytotoxicity. Results: SMI1182 and BEZ235, with or without DOX, significantly reduced directional motility. Combined treatments had additive cytotoxic effects linked to the reduced expression of ASPH, Notch transcription factors, and insulin receptor substrate type I, which positively regulates both ASPH and Notch. Conclusions: Triple-drug treatment with DOX, SMI1182, and BEZ235 could potentially improve disease-free survival with CS by the simultaneous targeting of multiple upstream mediators of aggressive malignant tumor cell behavior. Full article

To investigate the changes of ERα and PRs in the epithelium and stroma of normal and neoplastic uterine cervix. Two pathologists independently scored the expression levels of ERα, PR(A+B), and PRB in the stroma and epithelium of normal, cervical intraepithelial neoplasia grade 2 and 3 (CIN2/3), carcinoma in situ (CIS), and invasive cervical carcinoma (ICC) specimens. Sex hormone receptors were abundantly expressed in the stroma compared to the epithelium or carcinoma of the cervix. Stromal ERα was progressively upregulated during cervical carcinogenesis, with an immunoreactive score (IRS) of 1.3 ± 1.5, 2.1 ± 1.9, and 3.6 ± 3.3 in the CIN2/3, CIS, and ICC groups, respectively (p < 0.001). By contrast, epithelial PR(A+B) and PRB were downregulated, with IRS of 0.4 ± 0.7 and 0.5 ± 0.8, 0.1 ± 0.4 and 0.2 ± 0.6, and 0.1 ± 0.6 and 0.1 ± 0.4 in the CIN2/3, CIS, and ICC groups, respectively (p < 0.001). During the CIN2/3 transition, the coexpression relationship between ERα and PRs began to break down. Although epithelial PR(A+B) was downregulated, stromal PR(A+B) and PRB were upregulated with IRS of 2.0 ± 2.0 and 2.0 ± 1.9 as well as 2.1 ± 2.3 and 3.2 ± 3.2 in the CIS (p = 0.009) and ICC groups (p < 0.001), respectively. After complete transformation, the stromal PRB was significantly upregulated, and its loss was related to more distant metastasis and poorer prognosis. The results of this study highlight the carcinogenic role of stromal ERα, the tumor suppressor role of epithelial PRs, and the importance of stromal PRB in the development of cervical cancer; they can be used as a basis for developing prevention and treatment strategies for this disease. Full article

Background/Objectives: Yawning, a common physiological behavior, has emerged as a potential biomarker for drug responsiveness and side effects. This scoping review synthesizes current evidence on drug-induced yawning (DIY), focusing on its neurobiological mechanisms and clinical implications. Methods: A scoping review (INPLASY registration number: INPLASY202540048) was conducted using PubMed, Scopus, and Web of Science, including studies published in the past decade. The review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Handbook guidelines, ensuring systematic selection. Selected articles led to the analysis of 10 relevant studies encompassing 473 participants. Studies were evaluated for relevance to DIY, neurobiology, and clinical applications, with thematic analysis used to synthesize findings. Results: Four key themes emerged. (1) Yawning patterns: DIY involves frequent episodes (up to 80 yawns/day), varying by drug type and dosage. (2) Neurobiological mechanisms: Yawning is mediated by serotonin, dopamine, and oxytocin pathways, particularly via 5-HT2C and μ-opioid receptors. (3) Drug responsiveness: DIY is linked to SSRIs, opioids, and dopamine agonists. SSRIs induce yawning, while opioids suppress it, reflecting distinct neurochemical effects. (4) Clinical implications: Yawning may serve as a non-invasive biomarker for drug efficacy and side effects, particularly in opioid withdrawal and SSRI monitoring. Conclusions: DIY holds promise as a biomarker for drug safety and effectiveness, but research is limited by small sample sizes, methodological variability, and the absence of standardized yawning metrics. Future studies should establish consistent measures, account for interindividual variability, and evaluate DIY’s long-term clinical utility across diverse populations. Full article

Background: The role of CDK4/6 inhibitors (CDK4/6i) has expanded from the treatment of advanced breast cancer to early-stage disease, as recent studies have demonstrated their therapeutic benefits. However, evidence regarding the safety of combining CDK4/6i with adjuvant radiation therapy (RT) in a curative setting remains limited. This study aims to present clinical experiences of pulmonary toxicity following the combined use of adjuvant RT and CDK4/6i. Case presentation: We report a case of an Asian female with left breast cancer who underwent a modified radical mastectomy followed by adjuvant chemotherapy, RT, endocrine therapy, and CDK4/6i (abemaciclib) treatment. Cancer therapy-induced grade 2 pneumonitis was impressed by clinical signs and image findings. A 57-year-old postmenopausal woman was diagnosed with left breast invasive lobular carcinoma, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−), K67 index of 5–10%, and classified as pT3N3aM0 (stage IIIC). She received adjuvant chemotherapy with FEC followed by docetaxel, endocrine therapy with letrozole, and adjuvant RT of 50.4 Gy in 28 fractions to the left chest wall and regional nodal irradiation. Abemaciclib was initiated after completing RT. Treatment-related pneumonitis developed five months after RT and abemaciclib use. Conclusions: In breast cancer patients receiving a combination of RT and CDK4/6i as curative adjuvant treatment, pulmonary toxicity is a concern and requires careful monitoring, particularly in Asian populations. Full article

Cancer stem cells (CSCs) are described as a subpopulation of cells with capabilities of self-renewal, chemoresistance, and invasiveness. CSCs reside in tumor niches and can be studied in vitro through their enrichment in spheroids (Stem). Molecular iodine (I₂) induces apoptosis and differentiation in various cancer cells. I₂ can activate peroxisome proliferator-activated receptors type gamma (PPARγ), and its pathways are associated with its oxidant/antioxidant capacity. This work aimed to compare the effect of I₂ supplementation in progenitor and CSC populations with low (MCF-7 and S-K-NAS) and high invasiveness (MDA-MB231 and SK-N-BE2) in mammary and neuroblastoma (NB) cell lines. Results showed that the CSC population enriched by the spheroid culture overexpressed stem messengers CD44, SOX2, and NMYC and exhibited the highest mitochondrial metabolism (membrane mitochondrial potential and O₂⁻). The presence of I₂ increases PPARγ expression and induces apoptosis through the Bax/Bcl2 index in all populations but silences NMYC expression and reduces mitochondrial metabolism in Stem NB. I₂ also enhances the expression of nuclear erythroid factor 2 (Nrf2) in all populations, but the target antioxidant superoxide dismutase 2 (SOD2) is only elevated in progenitor cells. In contrast, the mitophagy inductors PTEN-induced putative kinase 1 (Pink1) and microtubule-associated protein1 light chain3 alpha (LC3) were overexpressed in Stem populations. I₂-preselected SK-N-BE2 populations exhibited minor implantation and invasion capacities in the in vivo zebrafish model. These data indicate that I₂ interferes with viability, implantation, and invasion capacity in all cell lines, but the molecular mechanisms vary depending on the progenitor or Stem condition. Full article