The role of ferroptosis in radiotherapy and combination therapy for head and neck squamous cell carcinoma (Review).

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive, heterogeneous tumour usually caused by alcohol and tobacco consumption, making it one of the most common malignancies worldwide. Despite the fact that various therapeutic approaches such as surgery, radiation therapy (RT), chemotherapy (CT) and targeted therapy have been widely used for HNSCC in recent years, its recurrence rate and mortality rate remain high. RT is the standard treatment choice for HNSCC, which induces reactive oxygen species production and causes oxidative stress, ultimately leading to tumour cell death. CT is a widely recognized form of cancer treatment that treats a variety of cancers by eliminating cancer cells and preventing them from reproducing. Immune checkpoint inhibitor and epidermal growth factor receptor are important in the treatment of recurrent or metastatic HNSCC. Iron death, a type of cell death regulated by peroxidative damage to phospholipids containing polyunsaturated fatty acids in cell membranes, has been found to be a relevant death response triggered by tumour RT in recent years. In the present review, an overview of the current knowledge on RT and combination therapy and iron death in HNSCC was provided, the mechanisms by which RT induces iron death in tumour cells were summarized, and therapeutic strategies to target iron death in HNSCC were explored. The current review provided important information for future studies of iron death in the treatment of HNSCC.

Association between the MDR1 rs1045642 polymorphism and breast cancer risk: An updated meta­analysis.

Multidrug resistance 1 (MDR1) is a transmembrane transporter on the cell membrane. As an ATP-dependent efflux pump, MDR1 is mainly responsible for the adsorption, distribution, metabolism, excretion and transportation of anticancer drugs to cancer cells. Mutations of the MDR1 gene may be associated with the incidence of cancer. In the past decade, associations found between the MDR1 rs1045642 polymorphism and breast cancer have been inconsistent and inconclusive. Therefore, the present study performed a meta-analysis including studies published up until August 16, 2023 to systematically evaluate the association between the MDR1 rs1045642 polymorphism and breast cancer risk. A total of 21 published case studies involving 6,815 patients with breast cancer and 9,227 healthy participants were included in the meta-analysis. Overall, the MDR1 rs1045642 polymorphism was not significantly associated with breast cancer-associated risk. However, in the subgroup analysis, the MDR1 rs1045642 polymorphism was found to be notably associated with a higher risk of breast cancer among Asian populations in recessive models [TT vs. CT + CC; odds ratio (OR)=1.393; 95% confidence interval (CI), 1.143-1.698; P=0.001; I2<25%]. The MDR1 C3435T polymorphism was also associated with a notable decrease in the incidence of breast cancer in mixed ethnicity populations (TT and CT + CC; OR=0.578; 95% CI, 0.390-0.856; P=0.006; I2<25%). In Caucasian populations, the MDR1 rs1045642 polymorphism was not associated with breast cancer risk. In conclusion, the present meta-analysis demonstrated that the MDR1 rs1045642 polymorphism may increase the risk of breast cancer in Asian populations, is associated with a reduced risk of breast cancer in mixed populations but has no notable effect in Caucasian populations.

Analytical evaluation of the automated genotyping system (GenPlex) compared to a traditional real-time PCR assay for the detection of high-risk human papillomaviruses.

The detection of high-risk human papillomaviruses (HPVs) is crucial for early screening and preventing cervical cancer. However, the substantial workload in high-level hospitals or the limited resources in primary-level hospitals hinder widespread testing. To address this issue, we explored a sample-to-answer genotyping system and assessed its performance by comparing it with the traditional real-time polymerase chain reaction (PCR) method conducted manually. Samples randomly selected from those undergoing routine real-time PCR detection were re-analyzed using the fully automatic GenPlex® system. This system identifies 24 types of HPV through a combination of ordinary PCR and microarray-based reverse hybridization. Inconsistent results were confirmed by repeated testing with both methods, and the κ concordance test was employed to evaluate differences between the two methods. A total of 365 samples were randomly selected from 7259 women. According to real-time PCR results, 76 were high-risk HPV negative, and 289 were positive. The GenPlex® system achieved a κ value greater than 0.9 (ranging from 0.920 to 1.000, p < 0.0001) for 14 types of high-risk HPV, except HPV 51 (κ = 0.697, p < 0.0001). However, the inconsistent results in high-risk HPV 51 were revealed to be false positive in real-time PCR by other method. When counting by samples without discriminating the high-risk HPV type, the results of both methods were entirely consistent (κ = 1.000, p < 0.0001). Notably, the GenPlex® system identified more positive cases, with 73 having an HPV type not covered by real-time PCR, and 20 potentially due to low DNA concentration undetectable by the latter. Compared with the routinely used real-time PCR assay, the GenPlex® system demonstrated high consistency. Importantly, the system's advantages in automatic operation and a sealed lab-on-chip format respectively reduce manual work and prevent aerosol pollution. For widespread use of GenPlex® system, formal clinical validation following international criteria should be warranted.

Investigating the shared genetic architecture between primary sclerosing cholangitis and inflammatory bowel diseases: a Mendelian randomization study.

BACKGROUND: Several studies have found that primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are closely associated. However, the direction and causality of their interactions remain unclear. Thus, this study employs Mendelian Randomization to explore whether there are causal associations of genetically predicted PSC with IBD. METHODS: Genetic variants associated with the genome-wide association study (GWAS) of PSC were used as instrumental variables. The statistics for IBD, including ulcerative colitis (UC), and Crohn's disease (CD) were derived from GWAS. Then, five methods were used to estimate the effects of genetically predicted PSC on IBD, including MR Egger, Weighted median (WM), Inverse variance weighted (IVW), Simple mode, and Weighted mode. Last, we also evaluated the pleiotropic effects, heterogeneity, and a leave-one-out sensitivity analysis that drives causal associations to confirm the validity of the analysis. RESULTS: Genetically predicted PSC was significantly associated with an increased risk of UC, according to the study (odds ratio [OR] IVW= 1.0014, P<0.05). However, none of the MR methods found significant causal evidence of genetically predicted PSC in CD (All P>0.05). The sensitivity analysis results showed that the causal effect estimations of genetically predicted PSC on IBD were robust, and there was no horizontal pleiotropy or statistical heterogeneity. CONCLUSIONS: Our study corroborated a causal association between genetically predicted PSC and UC but did not between genetically predicted PSC and CD. Then, we identification of shared SNPs for PSC and UC, including rs3184504, rs9858213, rs725613, rs10909839, and rs4147359. More animal experiments and clinical observational studies are required to further clarify the underlying mechanisms of PSC and IBD.

Akebia saponin D attenuates allergic airway inflammation through AMPK activation.

Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from Dipsacus asper Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200 µΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) (1 mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300 mg/kg) or AICAR (100 mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation.

Nasal spindle cell tumor: A case report and literature review.

BACKGROUND: Spindle cell tumors are rare and can occur in any organ or tissue. Due to their rarity the clinicopathological features and diagnostic protocols have not been adequately studied. However, it has become necessary to develop differential diagnosis of spindle cell tumors. Here, we report a case of a nasal spindle cell tumor diagnosed at our hospital in attempt to contribute to this gap in literature. KEY POINTS FROM THE CASE: A male in his 30s was admitted to our hospital with nasal obstruction that had persisted for several years. Electronic fibrolaryngoscopy revealed a smooth neoplasm within the nasal cavity. MAIN LESSONS TO BE LEARNED FROM THIS CASE REPORT: The results of this case emphasize that spindle cell tumors have large morphological variations, and it is difficult to determine the origin of tumor cells using hematoxylin and eosin staining alone. Therefore, it is necessary to improve the immunohistochemistry and combine it with clinical symptoms to diagnose the disease.

Extra villous trophoblast-derived PDL1 can ameliorate macrophage inflammation and promote immune adaptation associated with preeclampsia.

INTRODUCTION: Severe preeclampsia (sPE) is a systemic syndrome that may originate from chronic inflammation. Maintaining maternal-fetal hemostasis by the co-inhibitory molecule programmed death ligand 1 (PDL1) can be favorable for ameliorating inflammation from immune cells. Apart from programmed death 1 (PD1) expression, decidual macrophages (dMs) produce inflammatory cytokines, in response to cells which express PDL1. However, strong evidence is lacking regarding whether the PDL1/PD1 interaction between trophoblasts and decidual macrophages affects inflammation during sPE development. METHODS: To determine whether the trophoblast-macrophage crosstalk via the PDL1/PD1 axis modulates the inflammatory response in sPE-like conditions, at first, maternal-fetal tissues from sPE and normal patients were collected, and the PDL1/PD1 distribution was analyzed by Western blot, immunohistochemistry/ immunofluorescence and flow cytometry. Next, a coculture system was established and flow cytometry was used to identify how PDL1 was involved in macrophage-related inflammation under hypoxic stress. Transcriptional analysis was performed to clarify the inflammation-associated pathway induced by the PDL1/PD1 interaction. Finally, the Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) mouse model was used to examine the effect of PDL1 on macrophage-related inflammation by measuring PE-like symptoms. RESULTS: In maternal-fetal tissue from sPE patients, placental extravillous trophoblasts (EVTs) and dMs had a surprisingly increase of PDL1 and PD1 expression, respectively, accompanied by a higher percentage of CD68 +CD86 + dMs. In vitro experiments showed that trophoblast-derived PDL1 under hypoxia interacted with PD1 on CD14 +CD80 +macrophages, leading to suppression of inflammation through the TNFα-p38/NFκB pathway. Accordingly, the PE-like mouse model showed a reversal of PE-like symptoms and a reduced F4/80 + CD86 + macrophage percentage in the uterus in response to recombinant PDL1 protein administration, indicating the protective effect of PDL1. DISCUSSION: Our results initially explained an immunological adaptation of trophoblasts under placental hypoxia, although this protection was insufficient. Our findings suggest the possible capacity of modulating PDL1 expression as a potential therapeutic strategy to target the inflammatory response in sPE.

Non-targeted Profiling of Sea Buckthorn Fruit Oil Fingerprints from 3 Regions and Study on Its Antioxidant Activity.

This study investigated the chemical and volatile characteristics of sea buckthorn fruits from three different regions in China. The chemical composition of the volatile oil was determined by using a non-targeted gas chromatography and mass spectrometry (GC/MS) method and the differences in chemical composition among the three producing areas were compared by heatmap providing a visual basis for researchers. A total of 93 compounds were identified, including 52 compounds from the Northeast China, 51 from the Xinjiang region, and 37 from Inner Mongolia region. Then, the in vitro antioxidant activity of sea buckthorn fruit oil was measured using DPPH, ABTS, and SOD inhibition tests, and the results showed that sea buckthorn fruit oil in northeast China was the strongest antioxidant, followed by Inner Mongolia and Xinjiang. The results of the CCK-8 experiment indicated that within the tested concentration, there is no cell cytotoxicity of the essential oil in human umbilical vein endothelial cells (HUVECs) cells. The results could supply reference to distinguish sea buckthorn fruit from different production areas and, meanwhile, clarify the activity and safety of sea buckthorn oil.

Low-grade malignant myofibroblastic sarcoma of the larynx: a case report.

Low-grade myofibroblastic sarcoma (LGMS) is a rare malignant mesenchymal tumor derived from myofibroblasts. It is commonly identified in the head and neck, and particularly in the oral cavity, but rarely in the larynx. In this case report, we describe a patient who presented with hoarseness and underwent electronic fiber laryngoscopy, which revealed a neoplasm on the surface of his left vocal cord. The vocal cord tumor was resected under general anesthesia, and a malignant LGMS was diagnosed on postoperative pathologic examination. The results of immunohistochemical staining of the sections for vimentin (diffuse +), actin (partial +), and desmin (-) were consistent with this diagnosis. The patient recovered well after the surgery, and there was no recurrence of the neoplasm.

Role of Matrix Gla Protein in Transforming Growth Factor-ß Signaling and Nonalcoholic Steatohepatitis in Mice.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a complex disease involving both genetic and environmental factors in its onset and progression. We analyzed NASH phenotypes in a genetically diverse cohort of mice, the Hybrid Mouse Diversity Panel, to identify genes contributing to disease susceptibility. METHODS: A "systems genetics" approach, involving integration of genetic, transcriptomic, and phenotypic data, was used to identify candidate genes and pathways in a mouse model of NASH. The causal role of Matrix Gla Protein (MGP) was validated using heterozygous MGP knockout (Mgp+/-) mice. The mechanistic role of MGP in transforming growth factor-beta (TGF-ß) signaling was examined in the LX-2 stellate cell line by using a loss of function approach. RESULTS: Local cis-acting regulation of MGP was correlated with fibrosis, suggesting a causal role in NASH, and this was validated using loss of function experiments in 2 models of diet-induced NASH. Using single-cell RNA sequencing, Mgp was found to be primarily expressed in hepatic stellate cells and dendritic cells in mice. Knockdown of MGP expression in stellate LX-2 cells led to a blunted response to TGF-ß stimulation. This was associated with reduced regulatory SMAD phosphorylation and TGF-ß receptor ALK1 expression as well as increased expression of inhibitory SMAD6. Hepatic MGP expression was found to be significantly correlated with the severity of fibrosis in livers of patients with NASH, suggesting relevance to human disease. CONCLUSIONS: MGP regulates liver fibrosis and TGF-ß signaling in hepatic stellate cells and contributes to NASH pathogenesis.

Adult Nasopharyngeal Hamartoma: A Case Report.

Hamartomas are benign tumors characterized by an abnormal combination and arrangement of normal tissues during development. It is more common in lung, gastrointestinal tract and other parts, rare in the head and neck, such as oral cavity, nasal cavity, nasopharynx, etc. This case report describes a patient with nasopharyngeal hamartoma who presented with headache and rhinorrhea and was confirmed to have smooth nasopharyngeal neoplasm by electronic fibro laryngoscopy. After admission, the nasopharyngeal neoplasm was removed under general anesthesia and was postoperatively diagnosed as a hamartoma polyp. The patient recovered well postoperatively.

Effect of negative emotions on patients with advanced gastric cancer receiving systemic chemotherapy: a prospective study.

Background: Most patients with advanced gastric cancer (GC) are treated with systemic chemotherapy and many factors have remarkable impacts on their prognosis. However, the importance of psychological status in the prognosis of advanced GC patients is still unclear. This prospective study was performed to analyze the impact of negative emotions on GC patients treated with systemic chemotherapy. Methods: Advanced GC patients admitted to our hospital between January 2017 and March 2019 were prospectively enrolled. Demographic and clinical data were collected, as were any adverse events (AEs) related to systemic chemotherapy. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess negative emotions. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcome was the quality of life which was assessed by The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30. Cox proportional hazards models were used to analyze the effects of negative emotions on prognosis, and logistic regression models were used to analyze the risk factors related to negative emotions. Results: A total of 178 advanced GC patients were enrolled in this study. A total of 83 patients were divided into a negative emotion group and 95 patients were divided into normal emotion group. 72 patients experienced AEs during treatment. Many more patients experienced AEs in the negative emotion group than in the normal emotion group (62.7% vs. 21.1%, P<0.001). Enrolled patients were followed up for at least 3 years. It was found both PFS and OS were much lower in the negative emotion group than in the normal emotion group (P=0.0186 and 0.0387, respectively). Participants in negative emotion group had lower health status and more severe symptoms. Negative emotions, lower body mass index (BMI), and IV tumor stage were identified as risk factors. In addition, higher BMI and marital status were identified as protective factors of negative emotions. Conclusions: Negative emotions have a significant adverse effect on the prognosis of GC patients. The main risk factor of negative emotions is AEs during treatment. It is necessary to closely monitor the treatment process and improve the psychological status of patients.

Environmental Enrichment Protects Offspring of a Rat Model of Preeclampsia from Cognitive Decline.

Preeclampsia affects 5-7% of all pregnancies and contributes to adverse pregnancy and birth outcomes. In addition to the short-term effects of preeclampsia, preeclampsia can exert long-term adverse effects on offspring. Numerous studies have demonstrated that offspring of preeclamptic women exhibit cognitive deficits from childhood to old age. However, effective ways to improve the cognitive abilities of these offspring remain to be investigated. The aim of this study was to explore whether environmental enrichment in early life could restore the cognitive ability of the offspring of a rat model of preeclampsia and to investigate the cellular and molecular mechanisms by which EE improves cognitive ability. L-NAME was used to establish a rat model of preeclampsia. The spatial learning and memory abilities and recognition memory of 56-day-old offspring were evaluated by the Morris water maze and Novel object recognition (NOR) task. Immunofluorescence was performed to evaluate cell proliferation and apoptosis in the DG region of the hippocampus. qRT-PCR was performed to examine the expression levels of neurogenesis-associated genes, pre- and postsynaptic proteins and inflammatory cytokines. An enzyme-linked immune absorbent assay was performed to evaluate the concentration of vascular endothelial growth factor (VEGF) and inflammatory cytokines in the hippocampus. The administration of L-NAME led to increased systolic blood pressure and urine protein levels in pregnant rats. Offspring in the L-NAME group exhibited impaired spatial learning ability and memory as well as NOR memory. Hippocampal neurogenesis and synaptic plasticity were impaired in offspring from the L-NAME group. Furthermore, cell apoptosis in the hippocampus was increased in the L-NAME group. The hippocampus was skewed to a proinflammatory profile, as shown by increased inflammatory cytokine levels. EE improved the cognitive ability of offspring in the L-NAME group and resulted in increased hippocampal neurogenesis and synaptic protein expression levels and decreased apoptosis and inflammatory cytokine levels. Environmental enrichment resolves cognitive impairment in the offspring of a rat model of preeclampsia by improving hippocampal neurogenesis and synaptic plasticity and normalizing the apoptosis level and the inflammatory balance.

Amyloidosis in the nasopharynx and larynx: a case report.

Amyloidosis is a disease caused by amyloid deposition in tissues or organs. According to the extent of the lesion, it can be divided into systemic amyloidosis and localized amyloidosis. Amyloidosis originating in the larynx accounts for approximately 0.5% to 1.0% of benign lesions of the larynx; such lesions are relatively rare and mostly localized. Nasopharyngeal amyloidosis combined with laryngeal amyloidosis is even rarer. We herein present a case involving a patient with amyloidosis in the nasopharynx and larynx who presented with a foreign body sensation and hoarseness in the pharynx. Electronic fiber laryngoscopy revealed a smooth neoplasm in the left nasopharynx and left vocal cord. The patient underwent surgical treatment, and the postoperative pathologic examination results suggested amyloidosis. Special staining performed using Congo red and crystal violet was positive, confirming amyloidosis. The patient recovered after surgery, and no recurrence was present at the 3- and 6-month follow-ups.

Global burden of major gastrointestinal cancers and its association with socioeconomics, 1990-2019.

Background: To understand the impact of common cancers of the gastrointestinal tract and help to formulate evidence-based policy, we evaluate the relationship between the burden of GI tract cancers and socioeconomics. Methods: Data on GI tract cancer burden were obtained from the Global Burden of Disease (GBD) 2019 including mortality and incidence rates. According to the Socio-demographic Index (SDI) level, country and territory, and sex, etc., the data were further stratified. The association between the burden of GI tract cancer and socioeconomics, indicated by SDI, was described. Uncertainty analysis was estimated using bootstrap draw. Results: In 2019, five major cancers of the gastrointestinal tract led to an age-standardized incidence rate (ASIR) of 61.9 (95% CI 56.1-67.6) per 100 000 person-years. From 1990 to 2019, five common tumors of the gastrointestinal tract related age-standardized death rates (ASDRs) decreased by -22.7% (-31.1 to -13.5). For the five common tumors, ASIRs and ASDRs were both higher in males than those in females. Globally, Mongolia, and several East Asia countries exhibited the highest ASIRs in 2019. The high SDI, and high-middle SDI locations recorded the highest incidence rate and death rate of colon and rectum cancer and pancreatic cancer. On the contrary, the low-middle SDI, and low SDI locations possessed the highest incidence rate and death rate of stomach cancer and esophageal cancer. Conclusion: There is a profound association between socioeconomics and burden of common cancers of the gastrointestinal tract. It would be helpful for the high SDI, and high-middle SDI locations to pay special attention to the screening of colon and rectum cancer and pancreatic cancer while the low-middle SDI, and low SDI locations should pay more attention to the screening of stomach cancer and esophageal cancer.

Trophoblast Exosomal UCA1 Induces Endothelial Injury through the PFN1-RhoA/ROCK Pathway in Preeclampsia: A Human-Specific Adaptive Pathogenic Mechanism.

Preeclampsia is regarded as an evolution-related disease that has only been observed in humans and our closest relatives, and the important factor contributing to its pathogenesis is endothelial dysregulation secondary to a stressed placenta. Hypoxia-inducible factor 1 subunit alpha (HIF1α), a highly conserved molecule in virtually all mammals, is regarded as a crucial regulator of the hypoxia adaptation and evolution. Persistent high expression of HIF1α in the placenta is one of the pathogenic mechanisms of preeclampsia. Therefore, human-specific molecules should link increased HIF1α to preeclampsia. We reported that urothelial cancer associated 1 (UCA1) is a potential mediator because it is a human-specific long noncoding RNA (lncRNA) that is upregulated in placental tissues and maternal serum from women with preeclampsia and is regulated by HIF1α. The cellular HIF1α-UCA1 pathway promoted the adaptation of trophoblasts to hypoxia by inducing vascular endothelial growth factor (VEGF) secretion and changes in the levels of key enzymes in glycolysis. On the other hand, circulating exosomal UCA1 secreted from stressed trophoblasts induced vascular endothelial dysfunction, especially excess ROS production, as measured by exosome extraction and a coculture system. At the molecular level, UCA1 physically bound to ubiquitin-specific peptidase 14 (USP14), which is a deubiquitinating enzyme, and UCA1 functioned as a scaffold to recruit USP14 to profilin 1 (PFN1), an actin-binding protein contributing to endothelial abnormalities and vascular diseases. This ternary complex inhibited the ubiquitination-dependent degradation of PFN1 and prolonged its half-life, further activating the RhoA/Rho-kinase (ROCK) pathway to induce ROS production in endothelial cells. Taken together, these observations suggest a role for the evolution-related UCA1 in the HIF1α-induced adaptive pathogenic mechanism of preeclampsia, promoting the survival of hypoxic trophoblasts and injuring maternal endothelial cells.

A case of giant nasal septal angiomyolipoma.

Angiomyolipoma is an extremely rare, benign mesenchymal tumor of the nasal cavity, primarily common in the kidney and secondarily common in the liver. According to the author's knowledge, no cases of angiomyolipoma of the nasal septum have been identified to date. We report a case of a patient with a giant angiomyolipoma at the posterior end of the nasal septum who recovered after surgery without any complication.

Multinucleated Retinal Pigment Epithelial Cells Adapt to Vision and Exhibit Increased DNA Damage Response.

Multinucleated retinal pigment epithelium (RPE) cells have been reported in humans and other mammals. Rodents have an extremely high percentage of multinucleated cells (more than 80%). Both mouse and human multinucleated RPE cells exhibit specific regional distributions that are potentially correlated with photoreceptor density. However, detailed investigations of multinucleated RPE in different species and their behavior after DNA damage are missing. Here, we compared the composition of multinucleated RPE cells in nocturnal and diurnal animals that possess distinct rod and cone proportions. We further investigated the reactive oxygen species (ROS) production and DNA damage response in mouse mononucleated and multinucleated RPE cells and determined the effect of p53 dosage on the DNA damage response in these cells. Our results revealed an unrealized association between multinucleated RPE cells and nocturnal vision. In addition, we found multinucleated RPE cells exhibited increased ROS production and DNA damage after X-ray irradiation. Furthermore, haploinsufficiency of p53 led to increased DNA damage frequency after irradiation, and mononucleated RPE cells were more sensitive to a change in p53 dosage. In conclusion, this study provides novel information on in vivo PRE topography and the DNA damage response, which may reflect specific requirements for vision adaption and macular function.

Structural characterization and immunomodulatory activity of a mannan from Helvella leucopus.

A new polysaccharide fraction HLP-1 (2.55 × 105 Da) was obtained from the fruiting bodies of Helvella leucopus. Structural characterization of HLP-1 was elucidated by infrared spectroscopy, monosaccharide composition analysis, methylation analysis, nuclear magnetic resonance spectroscopy, scanning electron microscopy and Congo red assay. HLP-1 was a mannan with a backbone of →6)-α-D-Manp(1 â†’ 4)- α-D-Manp(1 â†’6)-α-D-Manp(1 â†’ 3)-α-D-Manp(1 â†’ 4)-α-D-Manp(1 â†’ 3)-α-D-Manp(1→, which branched at the O-6 position and terminated with T-ß-D-Manp. Moreover, HLP-1 could significantly improve the proliferation and neutral red phagocytosis of RAW264.7. Besides, HLP-1 could stimulate the production of nitric oxide (NO), ROS, tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6). HLP-1 induced macrophage activation via NF-κB signal pathway. These findings indicated that HLP-1 was a potential immune enhancement agent applied in functional foods.