Association of food insecurity with overall and disease-specific mortality among cancer survivors in the US.

PURPOSE: To investigate the association of food insecurity with overall and disease-specific mortality among US cancer survivors. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were used to examine the impact of food insecurity on mortality risks among cancer survivors in the US. Study participants aged ≥ 20 years who had a history of cancer and completed the Adult Food Security Survey Module were included. Mortality data [all-cause, cancer, and cardiovascular (CVD) specific] through December 31, 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazard regression, hazard ratios of mortality based on food security status were estimated. RESULTS: Among 5032 cancer survivors (mean age 62.5 years; 58.0% women; 86.2% non-Hispanic White), 596 (8.8%) reported food insecurity. Overall, 1913 deaths occurred (609 cancer deaths and 420 CVD deaths) during the median follow-up of 6.8 years. After adjusting for age, food insecurity was associated with a higher risk of overall (HR = 1.93; 95% CI = 1.56-2.39), CVD-specific (HR = 1.95; 95% CI = 1.24-3.05), and cancer-specific (HR = 1.70; 95% CI = 1.20-2.42) mortality (P < 0.001). However, after adjusting for socioeconomic characteristics and health-related factors (physical activity, diet quality measured by healthy eating index), the association between food insecurity and overall mortality was no longer statistically significant. CONCLUSIONS: Food insecurity was associated with a greater risk of overall mortality among cancer survivors. Further studies are needed to confirm these findings and evaluate whether the observed association represents a causal phenomenon and, if so, whether the effect is modifiable with food assistance programs.

Plasma-Activated Media Produced by a Microwave-Excited Atmospheric Pressure Plasma Jet Is Effective against Cisplatin-Resistant Human Bladder Cancer Cells In Vitro.

Media exposed to atmospheric pressure plasma (APP) produce reactive oxygen and nitrogen species (RONS), with hydrogen peroxide (H2O2), nitrite (NO2-), and nitrate (NO3-) being among the most detected species due to their relatively long lifetime. In this study, a standardized microwave-excited (ME) APP jet (APPJ) source was employed to produce gaseous RONS to treat liquid samples. The source was a commercially available plasma jet, which generated argon plasma utilizing a coaxial transmission line resonator at the operating frequency of 2.45 GHz. An ultraviolet-visible spectrophotometer was used to measure the concentrations of H2O2 and NO3- in plasma-activated media (PAM). Three different types of media (deionized water, Hank's balanced salt solution, and cell culture solution Dulbecco's modified eagles medium [DMEM]) were utilized as liquid samples. Among these media, the plasma-treated DMEM was observed to have the highest levels of H2O2 and NO3-. Subsequently, the feasibility of using argon ME-APPJ-activated DMEM (PAM) as an adjuvant to enhance the therapeutic effects of cisplatin on human bladder cancer cells (T-24) was investigated. Various cancer cell lines, including T-24 cells, treated with PAM were observed in vitro for changes in cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. A viability reduction was detected in the various cancer cells after incubation in PAM. Furthermore, the study's results revealed that PAM was effective against cisplatin-resistant T-24 cells in vitro. In addition, a possible connection between HER expression and cell viability was sketched.

Antidepressant effects of p-coumaric acid isolated from Vaccinium bracteatum leaves extract on chronic restraint stress mouse model and antagonism of serotonin 6 receptor in vitro.

BACKGROUND: Vaccinium bracteatum Thunb. leaves (VBL) are used in traditional herbal medicines to treat various biological diseases. p-coumaric acid (CA), the main active component of VBL, has neuroprotective effects against corticosterone-induced damage in vitro. However, the effects of CA on immobility induced by chronic restraint stress (CRS) in a mouse model and 5-HT receptor activity have not been investigated. HYPOTHESIS/PURPOSE: We investigated the antagonistic effects of VBL, NET-D1602, and the three components of Gαs protein-coupled 5-HT receptors. Additionally, we identified the effects and mechanism of action of CA, the active component of NET-D1602, in the CRS-exposed model. METHODS: For in vitro analyses, we used 1321N1 cells stably expressing human 5-HT6 receptors and CHO-K1 expressing human 5-HT4 or 5-HT7 receptors cell lines to study the mechanism of action. For in vivo analyses, CRS-exposed mice were orally administered CA (10, 50, or 100 mg/kg) daily for 21 consecutive days. The effects of CA were analyzed by assessing behavioral changes using a forced swim test (FST), measuring levels of hypothalamic-pituitary-adrenal (HPA) axis-related hormones in ntial therapeutic effects as 5-HT6 receptor antagonists for neurodegenerative diseases and depressioserum, and acetylcholinesterase (AChE), monoamines, including 5-HT, dopamine, and norepinephrine, using enzyme-linked immunosorbent assay kits. The underlying molecular mechanisms of the serotonin transporter (SERT), monoamine oxidase A (MAO-A), and extracellular signal-regulated kinase (ERK)/protein kinase B (Akt)/mTORC1 signaling were detected using western blotting. RESULTS: CA was confirmed to be an active component in the antagonistic effects of NET-D1602 on 5-HT6 receptor activity through decreases in cAMP and ERK1/2 phosphorylation. Moreover, CRS-exposed mice treated with CA showed a significantly reduced immobility time in the FST. CA also significantly decreased corticosterone, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) levels. CA enhanced 5-HT, dopamine, and norepinephrine levels in the hippocampus (HC) and prefrontal cortex (PFC) but decreased MAO-A and SERT protein levels. Similarly, CA significantly upregulated the ERK, Ca2+/calmodulin-dependent protein kinase II (CaMKII), Akt/mTOR/p70S6K/S6 signaling pathways in both HC and the PFC. CONCLUSION: CA contained in NET-D1602 may play the antidepressant effects against CRS-induced depression-like mechanism and the selective antagonist effect of 5-HT6 receptor.

A nurse-led intervention in patients with newly diagnosed cancer and Type 2 diabetes: A pilot randomized controlled trial feasibility study.

BACKGROUND: Undiagnosed Type 2 diabetes (T2D) has been associated with advanced stage cancer at diagnosis, higher mortality, and lower long-term all-cause survival. This was a RCT pilot study to examine the feasibility of a nurse-led T2D intervention for adults with newly diagnosed cancer (≤3 months), and T2D, undiagnosed or untreated with medication, conducted at an outpatient oncology clinic affiliated with a large academic institution. METHODS: Participants needed to meet the eligibility criteria including a HbA1c level between 6.5% and 9.9%. Randomization was 1:1 to a 3-month intervention that consisted of nursing-led diabetes education and immediate initiation of metformin versus referral to primary care for usual care (control). RESULTS: Three hundred and seventy nine patients were screened using EHR, 55 agreed to participate, and 3 had eligible HbA1c levels and were randomized in the study. Primary reasons for study exclusion included life expectancy ≤2 years (16.9%), current use or inability to tolerate metformin (14.8%), and abnormal labs that contraindicated metformin use (13.9%). CONCLUSION: This study was not feasible due to recruitment inefficiencies, but acceptable to all who qualified.

Neutrophil Extracellular Traps in Airway Diseases: Pathological Roles and Therapeutic Implications.

Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway diseases, including chronic rhinosinusitis, and suggests that targeting NETs could be a therapeutic strategy for airway diseases.

Effects of Neutrophil and Eosinophil Extracellular Trap Formation on Refractoriness in Chronic Rhinosinusitis With Nasal Polyps.

PURPOSE: This study investigated the clinical implications of neutrophil extracellular trap (NET) formation (NETosis) and eosinophil extracellular trap (EET) formation (EETosis) regarding refractoriness in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). METHODS: Nasal polyp specimens were obtained from 117 patients with CRSwNP who received endoscopic sinus surgery. Disease control status at postoperative 1 year was assessed. Refractory cases were defined as partly controlled or uncontrolled cases according to the EPOS 2020 guidelines. NETosis and EETosis were evaluated through immunofluorescence staining (citrullinated histone H3-human neutrophil elastase and citrullinated histone-galectin-10, respectively) followed by manual counting. The z-score of NET and EET counts was used to define the following four groups: low extracellular trap formation (ETosis), NETosis-predominant, EETosis-predominant, and high-ETosis. RESULTS: The refractory and non-refractory groups showed significant differences in the tissue eosinophil count (P = 0.005) and EET count (P = 0.029). The tissue neutrophil count and the NET/neutrophil ratio were significantly different between the refractory and non-refractory groups of patients with neutrophilic CRS (P = 0.045, 0.031, respectively). Refractoriness significantly differed among the low-ETosis (30.77%), NETosis-predominant (47.83%), EETosis-predominant (56.67%), and high-ETosis (83.33%) groups (P = 0.005). CONCLUSIONS: The results of this study suggest that tissue Eosinophilia and EETosis may play a prognostic role, primarily in CRSwNP and thattissue neutrophilia and NETosis can play as prognostic biomarkers in neutrophilic CRSwNP.

Limited English Proficiency and Screening for Cervical, Breast, and Colorectal Cancers among Asian American Adults.

BACKGROUND: Literature shows that limited English proficiency (LEP) influences individual healthcare-seeking behaviors. The Asian population is the fastest-growing racial/ethnic group in the US, and approximately 50% of foreign-born Asians are estimated to live with LEP. OBJECTIVE: To examine associations of LEP and patient-provider language concordance (PPLC) with evidence-based cancer screening utilization for cervical, breast, and colorectal cancers among Asian American adults. METHODS: We obtained LEP, PPLC, and up-to-date status on the three types of cancer screening from a nationally representative sample of Asian Americans aged ≥ 18 years in the 2010-2016 and 2018 Medical Expenditure Panel Surveys. We used multivariable logistic regression models with recommended survey weighting to examine associations of LEP and PPLC with the cancer screening uptake based on USPSTF guidelines. RESULTS: The study population comprised 8953 respondents, representing 8.17 million Asian American adults. Overall, 11.9% of respondents experienced LEP; of those with LEP, 20% were with PPLC. In multivariable models, compared to respondents without LEP, respondents with LEP and without PPLC were significantly less likely to report up-to-date status on breast (OR = 0.44; 95% CI: 0.26-0.76), cervical (OR = 0.44; 95% CI: 0.26-0.75), or colorectal cancer screening (OR = 0.46; 95% CI: 0.26-0.80). However, these differences were not detected in respondents with LEP and with PPLC. CONCLUSION: LEP is associated with lower up-to-date status on cancer screening among Asian Americans, while PPLC seems to moderate this association. These findings suggest the enhancement for language-appropriate and culturally competent healthcare for Asian Americans with LEP, which helps accommodate their communication needs and promotes cancer screening.

Examining the relationship between metformin dose and cancer survival: A SEER-Medicare analysis.

Cancer is a major health problem in the U.S and type 2 diabetes mellitus (T2DM) is known to increase the risk for the development of many cancers. Metformin, a first-line therapy for treating T2DM, is increasingly being used for its anticancer effects; however, the literature is limited on the effect of metformin dose on overall survival in patients with stage IV cancer. Overall survival was defined as the time interval from the date of diagnosis to the last known follow-up or death from any cause. Subjects who were alive on December 31, 2016 were censored. In this cohort study we examined the relationship between metformin dose and overall survival in persons with both T2DM and stage IV lung, breast, colorectal, prostate, or pancreas cancers. We used a retrospective study design with Cox proportional hazards regression analysis of the 2007-2016 of the Surveillance Epidemiology and End Results-Medicare (SEER) dataset. Of the 7,725 patients, 2,981(38.5%) had been prescribed metformin. Patients who used metformin had significantly better overall survival in both unadjusted (Unadjusted HR, 0.73; 95% CI, 0.69-0.76; p < 0.001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; p < 0.001). The overall survival between patients who took metformin with average daily dose ≥ 1000mg or < 1000mg were not statistically significant (aHR, 1.00; 95% CI, 0.93-1.08; p = 0.90). Metformin use regardless of dose is associated with increased overall survival in older adults with stage IV cancer.

Intraindividual Reliability of Opportunistic Computed Tomography-Assessed Adiposity and Skeletal Muscle Among Breast Cancer Patients.

BACKGROUND: Adiposity and skeletal muscle levels assessed on computed tomography (CT) scans are prognostic indicators for patients with breast cancer. However, the intraindividual reliability of temporal changes in body composition assessed on opportunistic CT scans is unclear. METHODS: This retrospective study included 50 patients newly diagnosed with breast cancer who had archived CT scans pre- and postsurgery for breast cancer. The third lumbar CT image was segmented for areas of 3 types of adipose tissues and 5 different densities of skeletal muscles. Mean and percent changes in areas pre- vs postsurgery were compared using Wilcoxon signed rank tests. Intraclass correlation coefficients (ICCs) with 95% confidence intervals were assessed. A 2-sided P less than .05 was considered statistically significant. RESULTS: Mean (SD) age at diagnosis was 58.3 (12.5) years, and the interval between CT scans was 590.6 (536.8) days. Areas for body composition components were unchanged except for intermuscular adipose tissue (mean change = 1.45 cm2, 6.74% increase, P = .008) and very high-density muscle (mean change = -0.37 cm2, 11.08% decrease, P = .01) during the interval. There was strong intraindividual reliability in adipose tissue and skeletal muscle areas on pre- vs postsurgery scans overall (ICC = 0.763-0.998) and for scans collected 3 or less years apart (ICC = 0.802-0.999; 42 patients). CONCLUSIONS: Although some body composition components may change after breast cancer surgery, CT scan assessments of body composition were reliable for a 3-year interval including the surgery. These findings inform measurement characteristics of body composition on opportunistic CT scans of patients undergoing surgery for breast cancer.

Plasma activated medium prepared by a bipolar microsecond-pulsed atmospheric pressure plasma jet array induces mitochondria-mediated apoptosis in human cervical cancer cells.

Plasma activated medium (PAM) was prepared by a bipolar microsecond-pulsed atmospheric pressure plasma jet (APPJ) array source and was utilized for cancer cell treatment. APPJ array-produced plasma were characterized. APPJ array treatment of three different solutions (deionized water (DW), HBSS (serum-free Hanks' balanced salt solution), and DMEM (Dulbecco's Modified Eagle Medium) + 10% FBS (fetal bovine serum)) were performed to induce the changes in the concentration of reactive oxygen and nitrogen species (RONS) as functions of the operating parameters. Human cervical cancer cells (HeLa) injected with plasma-treated media were investigated for changes in cell viability using MTT assay. It was observed that PAM-induced ROS can regulate the protein expression associated with mitochondria, and PAM causes apoptosis through Cyto C/JNK/p38 signaling on human cervical cancer cells.

Inhaled delivery of recombinant interferon-lambda restores allergic inflammation after development of asthma by controlling Th2- and Th17-cell-mediated immune responses.

Remarkable progress has recently been achieved to identify the biological function and potential value of novel therapeutic targets for the effective control of allergic asthma. Interferon (IFN)-λ has been suggested to restrict chronic inflammation in the lungs of asthmatic mice and we sought to determine the contribution of IFN-λ as an asthma therapeutic. We show that inhaled IFN-λ can restrict Th2 and Th17 inflammation in the lungs of asthmatic mice, accompanied with alteration of IL-10 secretion. BALB/C mice were used for an asthmatic mouse model with OVA. Recombinant IFN-λs (IFN-λ2: 2 µg, IFN-λ3: 2 µg) were inoculated into asthmatic mice after OVA challenge by intranasal delivery. Lungs of asthmatic mice were severely inflamed, with extensive inflammatory cell infiltration and increased goblet cell metaplasia with higher total lung resistance. Transcription of IL-4, IL-5, IL-13, and IL-17A was significantly higher until five days after the final OVA challenge. Asthmatic mice were administered recombinant IFN-λ via inhalation three times after the last challenge and the asthmatic mice showed improvement in lung histopathologic findings, and total lung resistance was maintained under normal range. IFN-λ inhalation exhibited significant decreases in Th2 and Th17 cytokine levels, and the populations of Th2 and Th17 cells were recovered from the lungs of asthmatic mice. Additionally, increase in IL-10 secretion from CD4 + Th cells population was observed in response to inhaled delivery of IFN-λ along with alterations in Th2 and Th17 cell-derived inflammation. Our findings show that inhaled delivery of IFN-λ can restrict airway inflammation in the lungs of asthmatic mice by controlling Th2- and Th17-mediated responses accompanied by regulation of IL-10 secretion even after asthma development.

Age-Related Increase of Collagen/Fibrin Deposition and High PAI-1 Production in Human Nasal Polyps.

Objective: Our previous studies showed an age-related increased prevalence of nasal polyps (NP) and reduced production of S100A8/9 in elderly patients with chronic rhinosinusitis with NP (CRSwNP). In this study, we investigated an unbiased age-related gene expression profile in CRSwNP subjects and healthy controls, and further identified the differences in their tissue remodeling. Methods: Microarrays using NP and uncinate tissues from health controls (elderly, age ≥65 vs. non-elderly, age 18-49) were performed, and differentially regulated genes were analyzed. Quantitative real-time PCR (qPCR), Immunostaining, Periodic acid-Schiff (PAS), trichrome staining, Western blot, and ELISA were performed for further investigation. Results: Microarrays identified differentially expressed genes according to disease and age; 278 in NP vs. controls, 75 in non-elderly NP vs. non-elderly controls, and 32 in elderly NP vs. elderly controls. qPCR confirmed that the PLAT gene was downregulated and the SERPINB2 gene upregulated in NP vs. controls. The serous glandular cell-derived antimicrobial protein/peptide-related genes such as BPIFB3, BPIFB2, LPO, and MUC7 were remarkably reduced in NP, regardless of age. SERPINE1 gene (plasminogen activator inhibitor-1, PAI-1) expression was significantly increased in elderly NP versus elderly controls. IHC and western blot confirmed significantly decreased production of MUC7 and LPO in NP versus controls. There was a trend of age-related reduction of submucosal gland cells in normal controls. Trichrome and immunofluorescence staining demonstrated an age-related increase of collagen and fibrin deposition in NP, consistent with increased PAI-1 production. Conclusion: This study demonstrated age-related differential glandular remodeling patterns and fibrosis in NP and normal controls. PAI-1 expression was significantly increased in elderly NP versus elderly controls, suggesting PAI-1 as a potential treatment target in elderly NP.

Associations of Computed Tomography Image-Assessed Adiposity and Skeletal Muscles with Triple-Negative Breast Cancer.

Obesity measured by anthropometrics is associated with increased risk of triple-negative breast cancer (TNBC). It is unclear to what extent specific adipose tissue components, aside from muscle, are associated with TNBC. This retrospective study included 350 breast cancer patients who received treatment between October 2011 and April 2020 with archived abdominal or pelvic computed tomography (CT) images. We measured the areas of adipose tissue and five-density levels of skeletal muscle on patients' third lumbar vertebra (L3) image. Logistic regression was performed to examine the associations of specific adiposity and skeletal muscles components and a four-category body composition phenotype with the TNBC subtype. Results showed that higher vs. lower areas (3rd vs. 1st tertiles) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were associated with increased odds of TNBC vs. non-TNBC after adjusting for age, race, stage, tumor grade, tumor size, and skeletal muscle areas (adjusted odds ratio [AOR], 11.25 [95% CI = 3.46-36.52]) and (AOR, 10.34 [95% CI = 2.90-36.90]) respectively. Higher areas of low density muscle was also associated with increased odds of TNBC (AOR, 3.15 [95% CI = 1.05-10.98]). Compared to normal body composition (low adipose tissue/high muscle), high adiposity/high muscle was associated with higher odds of TNBC (AOR, 5.54 [95% CI = 2.12-14.7]). These associations were mainly in premenopausal women and among patients with the CT performed after breast cancer surgery. Specific adipose tissue and low-density muscle can be associated with the TNBC subtype in breast cancer patients. The direction of association warrants confirmation by prospective studies.

Plasma-activated medium induces ferroptosis by depleting FSP1 in human lung cancer cells.

Cold atmospheric plasma (CAP) that generates reactive oxygen species (ROS) has received considerable scientific attentions as a new type of anticancer. In particular, an indirect treatment method of inducing cancer cell death through plasma-activated medium (PAM), rather than direct plasma treatment has been well established. Although various cell death pathways such as apoptosis, necroptosis, and autophagy have been suggested to be involved in PAM-induced cell death, the involvement of ferroptosis, another type of cell death regulated by lipid ROS is largely unknown. This study reports, that PAM promotes cell death via ferroptosis in human lung cancer cells, and PAM increases intracellular and lipid ROS, thereby resulting in mitochondrial dysfunction. The treatment of cells with N-acetylcysteine, an ROS scavenging agent, or ferrostatin-1, a ferroptosis inhibitor, protects cells against PAM-induced cell death. Interestingly, ferroptosis suppressor protein 1 (FSP1) is downregulated upon PAM treatment. Furthermore, the treatment of cells with iFSP1, an inhibitor of FSP1, further enhances PAM-induced ferroptosis. Finally, this study demonstrates that PAM inhibits tumor growth in a xenograft model with an increase in 4-hydroxynoneal and PTGS2, a byproduct of lipid peroxidation, and a decrease in FSP1 expression. This study will provide new insights into the underlying mechanism and therapeutic strategies of PAM-mediated cancer treatment.

CRISPR-Cas9 Gene Editing Protects from the A53T-SNCA Overexpression-Induced Pathology of Parkinson's Disease In Vivo.

Mutations in specific genes, including synuclein alpha (SNCA) that encodes the α-synuclein protein, are known to be risk factors for sporadic Parkinson's disease (PD), as well as critical factors for familial PD. In particular, A53T-mutated SNCA (A53T-SNCA) is a well-studied familial pathologic mutation in PD. However, techniques for deletion of the mutated SNCA gene in vivo have not been developed. Here, we used the CRISPR-Cas9 system to delete A53T-SNCA in vitro as well as in vivo. Adeno-associated virus carrying SaCas9-KKH with a single-guide RNA targeting A53T-SNCA significantly reduced A53T-SNCA expression levels in vitro. Furthermore, we tested its therapeutic potential in vivo in a viral A53T-SNCA-overexpressing rat model of PD. Gene deletion of A53T-SNCA significantly rescued the overexpression of α-synuclein, reactive microgliosis, dopaminergic neurodegeneration, and parkinsonian motor symptoms. Our findings propose CRISPR-Cas9 system as a potential prevention strategy for A53T-SNCA-specific PD.

Factors Associated with Thyroid-Related Adverse Events in Patients Receiving PD-1 or PD-L1 Inhibitors Using Machine Learning Models.

Targets of immune checkpoint inhibitors (ICIs) regulate immune homeostasis and prevent autoimmunity by downregulating immune responses and by inhibiting T cell activation. Although ICIs are widely used in immunotherapy because of their good clinical efficacy, they can also induce autoimmune-related adverse events. Thyroid-related adverse events are frequently associated with anti-programmed cell death 1 (PD-1) or anti-programmed cell death-ligand 1 (PD-L1) agents. The present study aims to investigate the factors associated with thyroid dysfunction in patients receiving PD-1 or PD-L1 inhibitors and to develop various machine learning approaches to predict complications. A total of 187 patients were enrolled in this study. Logistic regression analysis was conducted to investigate the association between such factors and adverse events. Various machine learning methods were used to predict thyroid-related complications. After adjusting for covariates, we found that smoking history and hypertension increase the risk of thyroid dysfunction by approximately 3.7 and 4.1 times, respectively (95% confidence intervals (CIs) 1.338-10.496 and 1.478-11.332, p = 0.012 and 0.007). In contrast, patients taking opioids showed an approximately 4.0-fold lower risk of thyroid-related complications than those not taking them (95% CI 1.464-11.111, p = 0.007). Among the machine learning models, random forest showed the best prediction, with an area under the receiver operating characteristic of 0.770 (95% CI 0.648-0.883) and an area under the precision-recall of 0.510 (95%CI 0.357-0.666). Hence, this study utilized various machine learning models for prediction and showed that factors such as smoking history, hypertension, and opioids are associated with thyroid-related adverse events in cancer patients receiving PD-1/PD-L1 inhibitors.

New onset of type 2 diabetes as a complication after cancer diagnosis: A systematic review.

BACKGROUND: Despite improved survival rates, cancer survivors are experiencing worse health outcomes with complications of treatment, such as type 2 diabetes mellitus (T2D), that may deteriorate survivorship. The purpose of this review was to provide a comprehensive review of T2D incidence following cancer diagnosis. METHODS: The study included: (1) cohort studies, (2) cancer diagnosis by a doctor, (3) incidence of T2D after diagnosis of cancer, and (4) adult patients over 18 years. Studies that focused on patients who had T2D as a preexisting condition at cancer diagnosis were excluded. RESULTS: Of a total of 16 studies, overall incidence of T2D ranged from 5.4% to 55.3%. The highest T2D incidence rate was observed in colorectal patients with cancer (53%). While results in prostate patients with cancer were mixed, patients who underwent androgen deprivation therapy (ADT) had a significantly higher incidence of new-onset T2D (12.8%, p = 0.01). Patients treated with chemotherapy within 1-5 years of initial diagnosis of colorectal cancer were at approximately 30% higher risk of T2D. One study found that 48% of T2D was preventable with optimal management during the process of patient care. CONCLUSION: Blood glucose management may allow physicians to intervene early and improve outcomes among patients with cancer.

Antipostmenopausal effects of Stauntonia hexaphylla and Vaccinium bracteatum fruit combination in estrogen-deficient rats.

BACKGROUND: Climacterium is a series of physical and mental symptoms occurring in women and men due to decreased levels of sex hormones. Women lose the ability to become pregnant due to decreased ovarian estrogen production; the initial symptom being hot flushes. In addition, urogenital atrophy, sexual dysfunction, mood changes, and osteoporosis occur. Extracts of Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) fruits, with a wide range of biological activities, are widely used in traditional herbal medicine. OBJECTIVE: The purpose of this study was to investigate the mitigation of menopausal symptoms, such as hot flushes and postmenopausal osteoporosis after combinatorial treatment with SH and VB (SHVB) of ovariectomized (OVX) rats. DESIGN: We measured the bone regenerative effect of SHVB on receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation in vitro and on ovariectomy-induced osteoporosis in vivo. We investigated the effect of SHVB in a rat model of menopausal hot flushes, in which the tail skin temperature increases following ovariectomy-induced rapid decline in estrogen levels. RESULTS: SHVB inhibited osteoclast formation and tartrate-resistant acid phosphatase activity in primary mouse bone marrow-derived cells. In an estrogen deficiency-induced rat model, measurement of serum bone turnover factors showed that treatment with SHVB lowered the increased bone turnover. Additionally, SHVB decreased OVX-induced bone loss of the total femur. SHVB inhibited osteoclast differentiation, prevented bone mass reduction, and improved trabecular bone structure and biochemical markers in OVX-induced osteoporosis. In addition, administration of SHVB significantly ameliorated the changes in skin temperature in OVX rats. CONCLUSION: SHVB improved the symptoms of menopause. These results provide the foundation for developing SHVB as a natural substance to replace hormones in the future.

Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa.

BACKGROUND: The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models. RESULTS: Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. CONCLUSION: Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.

Enhanced Type 2 Immune Reactions by Increased IL-22/IL-22Ra1 Signaling in Chronic Rhinosinusitis With Nasal Polyps.

PURPOSE: Recent studies have revealed the pathogenic role of interleukin (IL)-22 in atopic dermatitis and asthma. However, little is known about the role of IL-22 in the pathophysiology of chronic rhinosinusitis with nasal polyps. We aimed to investigate the expression of IL-22 and its pathogenic function in type 2 immune reactions of nasal polyps (NP). METHODS: Protein levels of inflammatory mediators were determined by multiplex immunoassay, and principal component analysis (PCA) was performed. Immunofluorescence analysis and mast cell culture were used to determine the cellular sources of IL-22. Normal human bronchial epithelial (NHBE) cells were stimulated using IL-22 in combination with diverse cytokines, and thymic stromal lymphopoietin (TSLP) was measured. RESULTS: IL-22 expression was not up-regulated in NP compared with control tissues, but IL-22-high NP revealed distinct features characterized by type 2 inflammatory cytokines such as chemokine (C-C motif) ligand (CCL)-11, CCL-24, and IL-5 on the PCA. Additionally, IL-22 positively correlated with type 2 immune mediators and the disease severity in NP. For the localization of the cellular sources of IL-22 in eosinophilic NP, it was expressed in cells mostly composed of eosinophil peroxidase-positive cells and partially of tryptase-positive cells. The human mast cell line, LAD2 cells, released IL-22 mediated by immunoglobulin E. Moreover, IL-22 receptor subunit alpha-1 (IL-22Ra1) expression was significantly increased in NP. IL-22Ra1 was up-regulated with poly(I:C) stimulation in NHBE cells. Furthermore, TSLP production was enhanced when stimulated with a combination of IL-13, poly(I:C), and IL-22. Treatment with anti-IL-22Ra1 also inhibited IL-22-induced enhancement of TSLP production. CONCLUSION: IL-22 was associated with type 2 inflammatory reactions in NP. The IL-22/IL-22Ra1 axis was enhanced and might be involved in type 2 inflammatory reactions via TSLP production in NP.