Snail extract for skin: A review of uses, projections, and limitations.

BACKGROUND: Snail mucin is becoming increasingly popular for its wide range of ingredients and potential benefits. Snail extract's widespread appearance in cosmetic formulations encourages an investigation into the medical and cosmetic benefits. AIMS: This study aims to explore current literature on the variety of snail mucin applications. Specifically, we present a review of the uses, global market estimates and projects, and limitations to snail mucin. METHODS: A literature search was conducted on PubMed reviewing snail mucin and their application in medical and dermatologic fields examining their uses. Economic reports were also investigated for Global Market estimates. RESULTS: The therapeutic use of snail mucin in medical fields has been studied as antimicrobial agents, drug delivery vehicles, antitumor agents, wound healing agents, and biomaterial coatings among others. Additionally, the use in cosmetic fields includes antiaging, hydrating, anti-acne, scarring, and hyperpigmentation treatments. It is important to highlight that most studies conducted were preclinical or small clinical studies, stressing the need for additional large-scale clinical trials to support these claims. Investigations into the global market found estimates ranging from $457 million to $1.2 billion with upward projections in the upcoming decade. Limitations include ethical habitats for collection, allergy investigation, and missing clinical studies. CONCLUSIONS: The findings presented here emphasize the expanding uses of snail mucin and its ingredients alongside a growing market cosmetic industry should consider. We also emphasize the need for appropriate clinical trials into the stated benefits of snail mucin to ensure consumer safety and ethical extraction of mucin.

Human Intestinal Defensin 5 Ameliorates the Sensitization of Colonic Cancer Cells to 5-Fluorouracil.

BACKGROUND AND AIM: The increasing dilemma of multidrug-resistant cancer cells in response to currently available chemotherapeutic drugs and their associated side effect(s), calls for the investigation of alternative anticancer advances and molecules. Therefore, the present study aimed to elucidate the combinatorial potential against colon cancer of human defensin 5 in combination with 5-fluorouracil (5-FU), and against 5-FU resistant colon tumor cells. METHODS: The in vivo combinatorial potential of HD-5 with 5-FU was elucidated in terms of tumor morphometrics, apoptosis assay, surface morphology histology of the colon(s), and transcriptional alterations. Changes in membrane dynamics with mucin expression were evaluated by fluorescence microscopy and histochemistry. The in vitro activity of the peptide/drug conjunction was explored by phase contrast microscopy, MTT, LDH assay, and AO/EtBr staining. Chemoresistance to 5-FU was determined by phase contrast microscopy, MTT assay, annexin V-FITC/PI flow cytometry, and MDR-1, Bak, and Bax expression. RESULTS: In vivo decreases in tumor parameters, with a marked increase in apoptosis and neutrophil infiltrations indicated restoration of normal architecture with improved mucin content in the treated colons. This happened with substantial changes in key molecular markers of the intrinsic apoptotic cascade. Membrane dynamics revealed that peptides and chemotherapeutic drugs could bind to cancerous cells by taking advantage of altered levels of membrane fluidity. CONCLUSION: Peptide treatment of drug-resistant Caco-2 cells promotes enhanced 5-FU uptake, in contrast to when cells were treated with 5-FU alone. Hence, HD-5 as an adjunct to 5-FU, exhibited strong cancer cell killing even against 5-FU-resistant tumorigenic cells.

Rhubarb extract rebuilding the mucus homeostasis and regulating mucin-associated flora to relieve constipation.

In clinical trials, rhubarb extract (Rb) was demonstrated to efficiently alleviate constipation. We would like to find out the underlying mechanism of rhubarb relieving constipation. However, there are few studies on the effects of rhubarb on colonic mucus secretion and constipation. The aim of this study was to investigate the effects of rhubarb on colonic mucus secretion and its underlying mechanism. The mice were randomly divided into four groups. Group I was the control group and Group II was the rhubarb control group, with Rb (24 g/kg body weight [b.w.]) administered through intragastric administration for three days. Group III mice were given diphenoxylate (20 mg/kg b.w.) for five days via gavage to induce constipation. Group IV received diphenoxylate lasting five days before undergoing Rb administration for three days. The condition of the colon was evaluated using an endoscope. Particularly, the diameter of blood vessels in the colonic mucosa expanded considerably in constipation mice along with diminishing mucus output, which was in line with the observation via scanning electron microscope (SEM) and transmission electron microscope (TEM). We also performed metagenomic analysis to reveal the microbiome related to mucin gene expression level referring to mucin secretion. In conclusion, Rb relieves constipation by rebuilding mucus homeostasis and regulating the microbiome.

Analysis of the efficacy of azelastine nasal spray combined with mussel mucin in the treatment of allergic rhinitis and the influence of peripheral blood CCL26 and CCR3 levels.

OBJECTIVE: A retrospective study was conducted to investigate the efficacy of azelastine nasal spray combined with mussel mucin in the treatment of allergic rhinitis (AR) and the effects of CCL26 and CC chemokine receptor-3 (CCR3). PATIENTS AND METHODS: A total of 80 patients with AR admitted to our hospital from March 2020 to March 2022 were included as the research objects. All subjects were divided into two groups according to the different therapeutic strategies by reviewing the patient's treatment. The control group (n = 40) was given azelastine nasal spray, while the study group (n = 40) was treated with a combination of mussel mucin and azelastine nasal spray. The clinical efficacy, clinical symptoms, and sleep quality improvement of the two groups were calculated and compared retrospectively. The serological indexes were compared, and the incidence of adverse reactions between the two groups was calculated retrospectively based on the patient's medical records. RESULTS: In the study and control groups, the effective rate was 95.00% and 72.50%. After treatment, the symptom scores of nasal congestions, nasal itching, sneezing, and runny nose and the total score of Pittsburgh sleep quality index (PSQI) in the study group were remarkably less. After treatment, the serum levels of sVCAM-1, interleukin-4 (IL-4), and immunoglobulin E (IgE) were decreased, and the levels of IL-12 were upregulated. Following treatment, Minimum nasal cross-section (NMCA) and total nasal resistance (TNR) at 75Pa in the study group were reduced more noticeably (p < 0.05). After treatment, the expression levels of CCL26 and CCR3 in peripheral blood were significantly decreased. In the control and study groups, the incidence of adverse reactions was 7.50% and 10.00%. CONCLUSIONS: Azelastine nasal spray combined with mussel mucin is effective in the treatment of allergic rhinitis, which can effectively improve patients' clinical symptoms, alleviate nasal ventilation disorders, reduce inflammatory reactions, and improve sleep quality. This strategy of combined treatment is safe and, therefore, worth advocating.

In vivo and In silico evidence of the protective properties of carvacrol against experimentally-induced gastric ulcer: Implication of antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Gastric ulcer is a serious disease that affects millions of individuals worldwide. Alcohol consumption is a major contributor to the disease pathogenesis and ethanol-induced ulcer in rats closely recapitulates the clinical pathology of ulcer. In this study, rats were pretreated with carvacrol (CAR,50 and 100 mg/kg, orally) 1 h before absolute ethanol administration to induce gastric ulcer. CAR prevented ethanol-induced increases in gastric volume and acidity while restored mucin content. The gastro-protective activity of CAR, particularly the higher dose (100 mg/kg), was further supported by histopathological examination, as manifested by reduced gastric lesions. Interestingly, oxidative stress is linked to early stages of ulcer development and progression. In this study, ethanol administration upregulated the levels of ROS-producing enzymes, NADPH oxidase homologs 1 and 4 (Nox1 and Nox4) and lipid peroxides while depleting the antioxidant defense mechanisms, including GSH, Glutathione Peroxidase (GPX) and catalase. Interestingly, these alterations were significantly ameliorated by CAR pretreatment. Additionally, CAR possesses anti-inflammatory and anti-apoptotic activities. Pretreatment with CAR blunted ethanol-induced increases in inflammatory cytokines (NF-κB and TNF-α) and rectified the apoptosis regulator (Bax/Bcl2 ratio) in gastric tissue. Moreover, the docking simulation of CAR illustrated good fitting and interactions with GPX, Nox1 and TNF-α through the formation of hydrogen and hydrophobic (pi-H) bonds with conservative amino acids, thus, further supporting the anti-inflammatory and antioxidant effects underlying the gastroprotective effects of CAR. In conclusion, this study elucidates, using in silico and in vivo models, that the gastroprotective activity of CAR is attributed, at least in part, to its mucin-secretagogue, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms.

Comparison of the immunotherapy efficacy between invasive mucinous and non-mucinous adenocarcinoma in advanced lung cancer patients with KRAS mutation: a retrospective study.

Invasive mucinous adenocarcinoma (IMA) is a rare variant of adenocarcinoma with unique clinical, radiological, and pathological features, among which KRAS mutation is the most common. However, the differences in the efficacy of immunotherapy between KRAS-positive IMA and invasive non-mucinous adenocarcinoma (INMA) patients remain unclear. Patients with KRAS mutated adenocarcinomas receiving immunotherapy between June 2016 and December 2022 were enrolled. Based on mucin-producing status, the patients were placed into two subgroups: the IMA group and INMA group. Patients with IMA were further classified into two subtypes according to the presence of mucin patterns: pure IMA (≥ 90%) and mixed mucinous/nonmucinous adenocarcinoma (≥ 10% of each histological component). Kaplan-Meier Curves and log-rank tests were used to analyze survival. Cox regression analysis of PFS were used to analyze the independent factors associated with efficacy. Sixty-five advanced adenocarcinoma patients with KRAS mutations received immunotherapy, including 24 patients with IMA and 41 with INMA. The median progression-free survival (PFS) was 7.7 months, whereas the median overall survival (OS) was 24.0 months. Significant difference in PFS could be observed in IMA and INMA (3.5 months vs. 8.9 months; P = 0.047). Patients with pure IMA tended toward prolonger survival in contrast to mixed mucinous/nonmucinous adenocarcinoma in PFS (8.4 months vs. 2.3 months; P = 0.349). The multivariable analysis demonstrated that IMA was an independent risk factor for PFS. In KRAS mutated patients, IMA was associated with poorer PFS after immunotherapy compared with INMA.

Validation of the AJCC 8th Edition Staging System for Disseminated Appendiceal Cancer Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-institutional Analysis.

BACKGROUND: The AJCC 8th edition stratifies stage IV disseminated appendiceal cancer (dAC) patients based on grade and pathology. This study was designed to externally validate the staging system and to identify predictors of long-term survival. METHODS: A 12-institution cohort of dAC patients treated with CRS ± HIPEC was retrospectively analyzed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed by using Kaplan-Meier and log-rank tests. Univariate and multivariate cox-regression was performed to assess factors associated with OS and RFS. RESULTS: Among 1009 patients, 708 had stage IVA and 301 had stage IVB disease. Median OS (120.4 mo vs. 47.2 mo) and RFS (79.3 mo vs. 19.8 mo) was significantly higher in stage IVA compared with IVB patients (p < 0.0001). RFS was greater among IVA-M1a (acellular mucin only) than IV M1b/G1 (well-differentiated cellular dissemination) patients (NR vs. 64 mo, p = 0.0004). Survival significantly differed between mucinous and nonmucinous tumors (OS 106.1 mo vs. 41.0 mo; RFS 46.7 mo vs. 21.2 mo, p < 0.05), and OS differed between well, moderate, and poorly differentiated (120.4 mo vs. 56.3 mo vs. 32.9 mo, p < 0.05). Both stage and grade were independent predictors of OS and RFS on multivariate analysis. Acellular mucin and mucinous histology were associated with better OS and RFS on univariate analysis only. CONCLUSIONS: AJCC 8th edition performed well in predicting outcomes in this large cohort of dAC patients treated with CRS ± HIPEC. Separation of stage IVA patients based on the presence of acellular mucin improved prognostication, which may inform treatment and long-term, follow-up strategies.

The Breast Cancer Single-Cell Atlas: Defining cellular heterogeneity within model cell lines and primary tumors to inform disease subtype, stemness, and treatment options.

PURPOSE: Breast Cancer (BC) is the most diagnosed cancer in women; however, through significant research, relative survival rates have significantly improved. Despite progress, there remains a gap in our understanding of BC subtypes and personalized treatments. This manuscript characterized cellular heterogeneity in BC cell lines through scRNAseq to resolve variability in subtyping, disease modeling potential, and therapeutic targeting predictions. METHODS: We generated a Breast Cancer Single-Cell Cell Line Atlas (BSCLA) to help inform future BC research. We sequenced over 36,195 cells composed of 13 cell lines spanning the spectrum of clinical BC subtypes and leveraged publicly available data comprising 39,214 cells from 26 primary tumors. RESULTS: Unsupervised clustering identified 49 subpopulations within the cell line dataset. We resolve ambiguity in subtype annotation comparing expression of Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 genes. Gene correlations with disease subtype highlighted S100A7 and MUCL1 overexpression in HER2 + cells as possible cell motility and localization drivers. We also present genes driving populational drifts to generate novel gene vectors characterizing each subpopulation. A global Cancer Stem Cell (CSC) scoring vector was used to identify stemness potential for subpopulations and model multi-potency. Finally, we overlay the BSCLA dataset with FDA-approved targets to identify to predict the efficacy of subpopulation-specific therapies. CONCLUSION: The BSCLA defines the heterogeneity within BC cell lines, enhancing our overall understanding of BC cellular diversity to guide future BC research, including model cell line selection, unintended sample source effects, stemness factors between cell lines, and cell type-specific treatment response.

Anti-inflammatory effects of medications used for viral infection-induced respiratory diseases.

Respiratory viruses like rhinovirus, influenza virus, respiratory syncytial virus, and coronavirus cause several respiratory diseases, such as bronchitis, pneumonia, pulmonary fibrosis, and coronavirus disease 2019, and exacerbate bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, and diffuse panbronchiolitis. The production of inflammatory mediators and mucin and the accumulation of inflammatory cells have been reported in patients with viral infection-induced respiratory diseases. Interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, and regulated on activation normal T-cell expressed and secreted are produced in the cells, including human airway and alveolar epithelial cells, partly through the activation of toll-like receptors, nuclear factor kappa B and p44/42 mitogen-activated protein kinase. These mediators are associated with the development of viral infection-induced respiratory diseases through the induction of inflammation and injury in the airway and lung, airway remodeling and hyperresponsiveness, and mucus secretion. Medications used to treat respiratory diseases, including corticosteroids, long-acting ß2-agonists, long-acting muscarinic antagonists, mucolytic agents, antiviral drugs for severe acute respiratory syndrome coronavirus 2 and influenza virus, macrolides, and Kampo medicines, reduce the production of viral infection-induced mediators, including cytokines and mucin, as determined in clinical, in vivo, or in vitro studies. These results suggest that the anti-inflammatory effects of these medications on viral infection-induced respiratory diseases may be associated with clinical benefits, such as improvements in symptoms, quality of life, and mortality rate, and can prevent hospitalization and the exacerbation of chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, and diffuse panbronchiolitis.

Silencing SOX11 Alleviates Allergic Rhinitis by Inhibiting Epithelial-Derived Cytokines

Background: Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa affecting the quality of life of patients. SRY-box transcription factor 11 (SOX11) was reported to play important roles in inflammatory responses, but its role in AR is poorly understood. Aims: To explore the role of SOX11 in the development of allergic rhinitis. Study Design: Cell culture and animal study. Methods: An in vivo murine allergic rhinitis model was established using ovalbumin treatment in female mice. Interleukin-13-stimulated human nasal mucosa epithelial cells were used for in vitro studies. Expression levels of SOX11, epithelial-derived cytokines, and mucin were determined in both modesls. Results: SOX11 was highly expressed in allergic rhinitis mice. Allergy symptoms, serum ovalbumin-specific IgE, histamine, eosinophils, goblet cells, and type 2 cytokine secretion were increased in ovalbumin-treated mice. Furthermore, allergic rhinitis mice exhibited overproduction of epithelial-derived cytokines (thymic stromal lymphopoietin, interleukin-25, interleukin-33), C-C motif chemokine ligand 26 (CCL26), and mucin 5 AC (MUC5AC). Silencing SOX11 alleviated the behavioral symptoms and upregulation of epithelial-derived cytokines, CCL26, and MUC5AC. In human nasal mucosa epithelial cells, interleukin-13 enhanced SOX11 expression in a time-dependent manner, and signal transducer and activator of transcription 6 (STAT6) was involved in the interleukin-13-mediated expression of SOX11 by regulating transcription. Knockdown of SOX11 reduced epithelial-derived cytokine expression and MUC5AC levels in interleukin-13-treated human nasal mucosa epithelial cells. Conclusion: SOX11 plays a critical role in allergic rhinitis development by regulating epithelial-derived cytokines and might be a new therapeutic target for allergic rhinitis.

[Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway].

This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.

Overexpression of Dehydrogenase/Reductase 9 Predicts Poor Response to Concurrent Chemoradiotherapy and Poor Prognosis in Rectal Cancer Patients.

Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed. Methods: Pearson's chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level. Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤ 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance. Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.

Oxysophocarpine inhibits airway inflammation and mucus hypersecretion through JNK/AP-1 pathway in vivo and in vitro.

Asthma is a high-incidence disease in the world. Oxysophocarpine (OSC), a quinolizidine alkaloid displays various pharmacological functions including anti-inflammation, neuroprotective, anti-virus and antioxidant. Here, we established mice and cell asthmatic model to explore the effects of OSC for asthma treatment. Mice were sensitized and challenged with ovalbumin (OVA) and treated with OSC before challenge. Enzyme-linked immuno sorbent assay (ELISA), hematoxylin and eosin (H&E), periodic acid-schiff (PAS), tolonium chloride staining and immunohistochemical assay were performed. OSC treatment inhibited inflammatory cell infiltration and mucus secretion in the airway, reduced IgE level in mouse serum and decreased IL-4, IL-5 production in bronchoalveolar lavage fluid (BALF). OSC also reduced the spleen index to regulate immune function. Meanwhile, NCI-H292 cells were induced by lipopolysaccharide (LPS) to simulate airway epithelial injury. OSC pretreatment decreased the IL-6 and IL-8 cytokine levels, mucin 5 AC expression, and mucin 5 AC mRNA level in the cell model. Further, OSC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), and activator protein 1 (AP-1, Fos and Jun). These findings revealed that OSC alleviated bronchial asthma associated with JNK/AP-1 signaling pathway.

Neoadjuvant chemotherapy improves survival in patients with oesophageal mucinous adenocarcinoma: Post-hoc analysis of the UK MRC OE02 and OE05 trials.

BACKGROUND: Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in detail. We hypothesised that patients with mucinous OeAC (OeACmucin) do not benefit from neoadjuvant chemotherapy. METHODS: OeAC patients either treated by surgery alone in the OE02 trial (S-patients) or by neoadjuvant chemotherapy followed by surgery (CS-patients) in OE02 or OE05 trials were included. Cancers from 1055 resection specimens (OE02 [test cohort]: 187 CS, 185 S; OE05 [validation cohort]: 683 CS) were classified as either mucinous (more than 50% of the tumour area consists of extracellular mucin, OeACmucin) or non-mucinous adenocarcinoma (OeACnon-mucin). The relationship between histological phenotype, clinicopathological characteristics, survival and treatment was analysed. RESULTS: Overall, 7.3% and 9.6% OeAC were classified as OeACmucin in OE02 and OE05, respectively. In OE02, the frequency of OeACmucin was similar in S and CS-patients. Patients with OeACmucin treated with surgery alone had a poorer overall survival compared with OeACnon-mucin patients (hazard ratio: 2.222, 95% confidence interval: 1.08-4.56, P = 0.025). Patients with OeACmucin treated with neoadjuvant chemotherapy and surgery had similar survival as OeACnon-mucin patients in test and validation cohort. CONCLUSIONS: This is the first study to suggest in a post-hoc analysis of material from two independent phase III clinical trials that the poor survival of patients with mucinous OeAC can be improved by neoadjuvant chemotherapy. Future studies are warranted to identify potential underlying biological, biochemical or pharmacokinetic interactions between extracellular mucin and chemotherapy.

Mucin-fused myeloid-derived growth factor (MYDGF164) exhibits a prolonged serum half-life and alleviates fibrosis in chronic kidney disease.

BACKGROUND AND PURPOSE: Although no effective therapy is available to stop or reverse CKD progression targeting its key feature, the loss of peritubular capillaries (PTCs) leading to interstitial fibrosis, myeloid-derived growth factor (MYDGF) with tissue-repairing activities enlightens its therapeutic potential for CKD. However, the extremely short circulatory lifetime (15 min) restricts its application. EXPERIMENTAL APPROACH: We selected a tandem repeated (TR) region of human CD164 as a carrier to fuse with MYDGF and then investigated for biophysical and pharmacokinetic changes. The MYDGF164 bioactivities were validated in HUVECs and then assessed in HK-2 cells. We also investigated its efficacy in unilateral ureteral obstruction (UUO)-treated mice and in adenine-induced CKD rats. KEY RESULTS: MYDGF164 was modified with sialoglycans, improving its resistance to serum proteases and increasing its hydrodynamic radius. The half-life of MYDGF164 was significantly prolonged but retained its original cell proliferation, anti-apoptosis, and tubulogenesis activities. It selectively stimulated the proliferation in endothelial and epithelial cells through phosphorylating MAPK1/3. MYDGF164 alleviated capillary rarefaction, hypoxia, renal fibrosis, and tubular atrophy in UUO mice and in adenine-induced CKD rats. MYDGF164 restored renal function, with normalized creatinine and urea levels in adenine-induced CKD rats. Histopathology and immunohistochemistry revealed that MYDGF164 protection was related to its cell-proliferative, anti-apoptosis, and angiogenesis activities. CONCLUSIONS AND IMPLICATIONS: This study is the first successful example of using a tandem repeated region of hCD164 as a cargo protein for the pharmacokinetic improvement of therapeutic proteins. Our findings highlight the potential of MYDGF164 in alleviating renal fibrosis in CKD.

Small lymphocytic lymphoma presenting as chronic diffuse lip swelling.

Although rare, small lymphocytic lymphoma can present as chronic lip swelling and papules, thus mimicking the features of orofacial granulomatosis, a chronic inflammatory disorder characterized by subepithelial noncaseating granulomas, or papular mucinosis, characterized by localized dermal mucin deposition of mucin. When assessing lip swelling, one must carefully consider the clinical clues and have a low threshold to perform a diagnostic tissue biopsy, preventing delays in treatment or progression of the lymphoma.

Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth.

Growing evidence supports the importance of gut microbiota in the control of tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa that promote anti-tumor immunity. Addition of the prebiotics inulin or mucin to the diet of C57BL/6 mice induces anti-tumor immune responses and inhibition of BRAF mutant melanoma growth in a subcutaneously implanted syngeneic mouse model. Mucin fails to inhibit tumor growth in germ-free mice, indicating that the gut microbiota is required for the activation of the anti-tumor immune response. Inulin and mucin drive distinct changes in the microbiota, as inulin, but not mucin, limits tumor growth in syngeneic mouse models of colon cancer and NRAS mutant melanoma and enhances the efficacy of a MEK inhibitor against melanoma while delaying the emergence of drug resistance. We highlight the importance of gut microbiota in anti-tumor immunity and the potential therapeutic role for prebiotics in this process.

Iron Pharmacokinetics in Women with Iron Deficiency Anaemia Following A Single Oral Dose of a Novel Formulation of Tardyferon (Prolonged Release Ferrous Sulphate).

Numerous iron-containing preparations are available on the market; these vary in dosage, salt, chemical state of iron (ferric or ferrous) and in the iron delivery process (immediate or prolonged-release). Tardyferon® is a prolonged-release tablet containing 80 mg ferrous sulphate. The formulation has recently been modified; changes to the excipients which constitute the inert formulation matrix have allowed a decrease in tablet size for easier swallowing. The aim of this multicenter open-label study was to characterize the serum pharmacokinetics of iron in non-pregnant women aged 23-45 years with iron deficiency anaemia (IDA) following single oral administration of 160 mg Tardyferon® under fasting conditions. Blood samples were collected from the 29 participants before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method; pharmacokinetic parameters were derived using a non-compartmental approach. In these patients, median time to maximum serum concentrations (Tmax) was 4 h. Serum profiles were consistent with prolonged release; iron levels were elevated up to 12 h after dosing, with mean C12h still more than 7 times higher than baseline (CT0), and mean C2h and C8h representing 69.7% and 81.9% of the Cmax, respectively. In vitro dissolution testing performed on the clinical batch also demonstrated prolonged release of iron from this formulation. A single oral dose of 160 mg Tardyferon® administered under fasting conditions to this target population resulted in a long-lasting release of iron in the gastrointestinal tract, leading to optimal iron absorption. Moreover, Tardyferon® was well tolerated.

Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration.

Gold nanotheranostics: photothermal therapy and imaging of Mucin 7 conjugated antibody nanoparticles for urothelial cancer.

OBJECTIVE: To kill urothelial cancer cells while preserving healthy cells, this study used photothermal therapy (PTT). PTT techniques target urothelial cancer cells using gold nanoparticles (GNPs) and a green light laser. MATERIALS AND METHODS: The GNPs were conjugated with anti-Mucin 7 antibodies, which acted as a probe for targeting tumor cells. Conjugated GNPs were exposed to a green light laser (532 nm) with sufficient thermal energy to kill the transitional cell carcinomas (TCCs). RESULTS: According to our results, nanoparticles conjugated with Mucin 7 antibodies damaged all types of cancer cells (MBT2, T24, 9202, and 8301) at relatively low energy levels (i.e., 500 laser shots at 10 W/cm(2) in power, 1.6 Hz in frequency, and 300 ms in duration). Nonconjugated nanoparticles required 30 W/cm(2) or more to achieve the same effect. Cell damage was directly related to irradiation time and applied laser energy. CONCLUSIONS: The minimally invasive PTT procedure combined with Mucin 7 targeted GNPs is able to kill cancer cells and preserve healthy cells. The success of this treatment technique can likely be attributed to the lower amount of energy required to kill targeted cancer cells compared with that required to kill nontargeted cancer cells. Our in vitro pilot study yielded promising results; however, additional animal studies are required to confirm these findings.