A persistent level of Cisd2 extends healthy lifespan and delays aging in mice.

The CISD2 gene, which is an evolutionarily conserved novel gene, encodes a transmembrane protein primarily associated with the mitochondrial outer membrane. Significantly, the CISD2 gene is located within the candidate region on chromosome 4q where a genetic component for human longevity has been mapped. Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in premature aging in mice. Additionally, an age-dependent decrease in Cisd2 expression has been detected during normal aging. In this study, we demonstrate that a persistent level of Cisd2 achieved by transgenic expression in mice extends their median and maximum lifespan without any apparent deleterious side effects. Cisd2 also ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. These results suggest that Cisd2 is a fundamentally important regulator of lifespan and provide an experimental basis for exploring the candidacy of CISD2 in human longevity.

Characterization of the components in plasma EVs unveiling the link between EVs-derived complement C3 with the severity and initial treatment response of profound sudden sensorineural hearing loss.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is characterized by rapid, unexplained loss of hearing within a 72-hour period and exhibits a high incidence globally. Despite this, the outcomes of therapeutic interventions remain largely unpredictable, especially for those with profound hearing loss. Extracellular vesicles (EVs), nano-sized entities containing biological materials, are implicated in the development of numerous diseases. The specific relationship between EVs and both the severity and treatment effectiveness of SSNHL, however, is not well understood. METHODS: This study involved the analysis of medical records from the Department of Otolaryngology (September 1, 2020 - December 31, 2022) of patients diagnosed with SSNHL according to the 2015 Guidelines for Diagnosis and Treatment of Sudden Deafness in China. Peripheral blood samples from patients with various types of SSNHL before and after treatment were collected, alongside samples from healthy volunteers serving as controls. Plasma EVs were isolated using gel rejection chromatography and analyzed for concentration, marker presence, and morphology using Nanosight, Western blot, and transmission electron microscopy (TEM), respectively. Proteomics and miRNA assessments were conducted to identify differentially expressed proteins and miRNAs in the plasma EVs of SSNHL patients and healthy volunteers. Key proteins were further validated through Western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was utilized to determine the levels of complement C3 in plasma EVs, and correlation analyses were performed with audiological data pre- and post-treatment. RESULTS: Plasma from SSNHL patients of varying types was collected and their EVs were successfully isolated and characterized. Proteomic analysis revealed that complement C3 levels in the plasma EVs of patients with profound SSNHL were significantly higher compared to healthy controls. Differential expression of miRNAs in plasma EVs and their related functions were also identified. The study found that the level of complement C3 in plasma EVs, but not the total plasma complement C3, positively correlated with the severity of SSNHL in patients exhibiting positive therapeutic responses, particularly in those with initially lower levels of EV-associated complement C3. After treatment, complement C3 level was decreased in patients with initially higher levels of EV-associated complement C3. No significant correlation was observed between changes in plasma EV-derived complement C3 levels and the degree of hearing loss in either responders or non-responders among patients with profound SSNHL. CONCLUSION: Differential profiles of proteins and miRNAs were identified in patients with profound SSNHL. Notably, plasma EV-derived complement C3 was linked to both the severity and early treatment effectiveness of patients with profound SSNHL.

DJ-1: a novel independent prognostic marker for survival in glottic squamous cell carcinoma.

DJ-1 is frequently overexpressed in a large variety of solid tumors, but the DJ-1 expression in laryngeal squamous cell cancer and its clinical/prognostic significance is unclear. We aimed to evaluate DJ-1 protein expression in glottic squamous cell carcinoma (GSCC) and to correlate this with clinicopathological data including patient survival. The expression of DJ-1 in GSCCs (60) and adjacent normal tissue (44) was assessed by immunohistochemistry and western blot analysis. In addition, the role of DJ-1 was investigated in tumorigenesis by transfecting DJ1-specific siRNA into laryngeal squamous cell carcinoma (LSCC) Hep-2 cells. Our data showed that positive expression of DJ-1 was found in 85% of GSCCs. In univariate survival analysis of the GSCC cohorts, a highly significant association between DJ-1 expression with shortened patient overall survival (5-year survival rate 92.9%vs 66.6%; P = 0.001; log rank test) was demonstrated. In multivariate analyses, DJ-1, tumor grading, and pT status were significant prognostic parameters for shortened patient overall survival. Furthermore, siRNA targeting DJ-1 can effectively inhibit DJ-1 expression, resulting in enhanced apoptosis and less proliferation of Hep-2 cells. We concluded that DJ-1 overexpression might be a novel independent molecular marker for poor prognosis (shortened overall survival) of patients with GSCC.

Protection of rats spinal cord ischemia-reperfusion injury by inhibition of MiR-497 on inflammation and apoptosis: Possible role in pediatrics.

MicroRNAs are extensively included in the pathogenesis and progression of many diseases by inhibiting target gene expression. Recently, studies have demonstrated that microRNA-497 (miR-497) may be implicated in human breast cancer that miR-497 predicts the prognosis of breast cancer patients from the posttranscriptional level. However, the specific function of miR-497 in spinal cord ischemia-reperfusion (IR) injury is far from clear nowadays. The present study was designed to determine the role of miR-497 in spinal cord IR injury and investigate the underlying spinal cord protective mechanism. The rat spinal cord IR injury model was performed by occluding the left anterior descending coronary artery for 30 min, which is then followed by 12h reperfusion. As predicted, miR-497 over-expression markedly decreased the expression of IL-1 receptor associated kinase (IRAK1) and Cyclic AMP response element binding protein (CREB). Moreover, Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and Caspase-3, as miR-497 potential targets were significantly suppressed after miR-497 transfection, then preventing inflammatory cytokines and factors regulating apoptosis. We also found that tumor necrosis factor-a (TNF-α) and interleukin-1beta (IL-1ß) activity, pro-apoptotic related genes, such as extracellular regulated protein kinases (ERK), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL levels were all decreased associated with the down-regulation of IRAK1 and CREB. In conclusion, our data demonstrate that miR-497 could inhibit inflammation and apoptosis of spinal cord IR through its targets, IRAK1 of TLR4 and CREB signaling pathway. Thus, miR-497 may constitute a new therapeutic target for the prevention of spinal cord IR injury.

DJ-1-induced phosphatase and tensin homologue downregulation is associated with proliferative and invasive activity of laryngeal cancer cells.

DJ-1, a novel mitogen-dependent oncogene, has an important role in the progression of human malignancies, whereas tumor suppressor phosphatase and tensin homolog (PTEN) is known to control a variety of processes associated with cell survival, proliferation and invasion. DJ-1 overexpression was reported to be negatively correlated with PTEN expression in tumor tissues of patients with laryngeal squamous cell carcinoma (LSCC). In the present study, the effect of DJ-1 on PTEN in laryngeal cancer cells was investigated by transfecting DJ-1-specific small interfering (si)RNA into Hep-2 and SNU-899 cells. Cell survival and cell proliferative and invasive capacity were then evaluated. The results showed that siRNA targeting of DJ-1 effectively upregulated PTEN expression, resulting in enhanced cell death as well as decreased proliferation and invasion of Hep-2 and SNU-899 cells. The results of the present study indicated, for the first time, to the best of our knowledge, that DJ-1-induced PTEN downregulation is associated with proliferative and invasive activity of laryngeal cancer cells. The DJ-1 gene may have an important role in the tumorigenesis of LSCC.

Mutagenicity and genotoxicity effects of Lignosus rhinocerotis mushroom mycelium.

ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerotis mushroom is widely used as traditional medicine and as soup ingredient in Malaysia and Hong Kong. Its sclerotium is the part of edibility and is traditionally used for the treatment of fever, cough, asthma and cancer. In view of its safety profile, very little information is found in scientific literature. MATERIALS AND METHODS: We evaluated the potential genotoxic and mutagenic effects of Lr in the Ames test using Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537, an in vitro chromosome aberration test in Chinese Hamster Ovary (CHO-K1) cells and an in vivo erythrocyte micronucleus test in ICR mice. RESULTS: In all tested concentrations, no mutagenicity was observed in either testing strain under both presence and absence of S9 metabolic mixture when tested up to the highest dose of 100mg/ml. No significant increases in chromosome aberration numbers or micronucleated polychromatic erythrocytes were observed. Erythropoiesis was not affected in animals gavaged up to 2000 mg/kg of Lr. CONCLUSIONS: Results from this study conclude that Lignosus rhinocerotis mycelium does not provoke mutagenicity and genotoxicity in these applied systems.

Biological characteristics of CD133(+) cells in nasopharyngeal carcinoma.

Cancer stem cells are regarded as the cause of tumour formation and recurrence in nasopharyngeal carcinoma (NPC). However, ideal surface markers for stem cells in NPC remain unidentified. In the present study, we investigated the expression of CD133, Nanog and Sox2 in the nasopharyngeal carcinoma cell line CNE2 and primarily cultured NPC cells using immunofluorescence or flow cytometry. A cell population with a CD133(+) phenotype was enriched using magnetic-activated cell sorting technology. We demonstrated that CD133(+) cells exhibited a strong potential for self-renewal, proliferation and differentiation and a greater potential for in vivo tumour formation in nude mice compared to CD133(-) cells, although the percentage of CD133(+) cells was small. However, the specific marker antigens Nanog and Sox2 were simultaneously expressed in normal cancer stem cells. Our results showed that CD133 can serve as a specific surface marker for nasopharyngeal cancer stem cells.

Tumorigenesis role and clinical significance of DJ-1, a negative regulator of PTEN, in supraglottic squamous cell carcinoma.

BACKGROUND: DJ-1 can induce the tumor cell proliferation and invasion via down-regulating PTEN in many malignant tumors, and correlated to prognostic significance. However, the tumorigenesis role and clinical significance of DJ-1 in supraglottic squamous cell carcinoma (SSCC) is unclear. We aimed to evaluate the DJ-1 the relationship between DJ-1 and clinicopathological data including patient survival. METHODS: The expression of DJ-1 and PTEN in SSCCs (52) and adjacent non-cancerous tissues (42) was assessed by immunohistochemistry (IHC), and the relationship between DJ-1 and clinicopathological data was analyzed. RESULTS: DJ-1 was detected mainly in SSCCs (88.5%) and less frequently in adjacent non-cancerous tissues (21.0%). PTEN expression was detected in 46.2% of SSCCs and in 90.5% of adjacent non-cancerous tissues. DJ-1 expression was linked to nodal status (P = 0.009), a highly significant association of DJ-1 expression with shortened patient overall survival (5-year survival rate 88.0% versus 53.9%; P = 0.007; log rank test) was demonstrated. CONCLUSIONS: Our data suggested that DJ-1 over-expression was linked to nodal status, and might be an independent prognostic marker for patients with SSCC.

[A comparative study on numerical simulation of the normal nasal airflow during periodic breathing and steady-state breathing].

OBJECTIVE: To compare the characteristics of normal nasal airflow during periodic breathing and steady-state breathing. METHODS: Fluent software was used to simulate the nasal cavity and paranasal sinus structures following CT scanning of a normal adult subject. Air flow velocity, pressure, distribution and streamlines were calculated and compared during periodic breathing and steady-state breathing. RESULTS: The same flux, the performance of nasal airflow on 15.600 s of periodic breathing and steady-state expiratory (entrance flow was 697.25 ml/s) were as follows: air flow in the common and middle meatus accounted for more than 50% and 30% of total nasal cavity flow during two respiratory status. Flow velocity and pressure of nasal cavity and each paranasal sinus were extremely similar. The flow trace during two respiratory status in the inferior and lower part of the common meatus were predominately straight in form.Flow were parabolic in the middle and superior meatus and the middle and upper parts of the common meatus. The flow trace of nasal airflow on 16.495 s of periodic breathing had wide areas vortex in nasopharynx and limen nasi, the average speed was 0.0706 m/s, while the entrance flow 7.62 ml/s stable state of the left nasal expiratory, the average speed was 0.0415 m/s, the flow trace was similar to 697.25 ml/s. CONCLUSION: The same flow, except in the junction of the respiratory cycle, the performance of normal nasal airflow during periodic breathing and steady-state breathing were similar.

[Diagnosis and treatment of traumatic delayed cerebrospinal fluid rhinorrhea].

OBJECTIVE: To explore the etiological factor, diagnostic localization and treatment of delayed cerebrospinal fluid (CSF) rhinorrhea. METHODS: The medical records of 79 patients who had undergone endoscopic repair of CSF rhinorrhea between 2000 and 2008 were reviewed. Thirteen patients with CSF leaks occurred 3 months after head trauma. All 13 patients with delayed CSF leak were retrospectively evaluated with CT or MRI and surgically treated. The operative findings were compared with the results of CT or MRI to estimate the diagnostic value of imaging technique. RESULTS: Bony defects had been found on CT scanning in all 13 patients. Neural tissue herniation into the nasal sinuses was found in 11 patients during the surgery. The sizes of the leak ranged from 0.1 cm x 0.2 cm to 1.2 cm x 1.5 cm. Reconstruction of the skull base was done through endoscopic approach. No complications were found. Thirteen patients were followed up from 12 - 36 months, and none was recurrence. CONCLUSIONS: Herniation of mucosal tissue into the nasal sinuses after skull base defects could result in delayed CSF leak. CT and MRI can clearly show the skull base defects and neural tissue herniation. Endoscopic closure of CSF leaks was both safe and effective.

[Investigation of intranasal bacteriological character and pH value in patients with chronic rhinitis treated by Budesonide aqueous nasal spray].

OBJECTIVE: To investigate the bacteriological character and pH value in nasal cavity and observe the efficacy following 8 week treatment with Budesonide aqueous nasal spray in chronic nonallergic rhinitis. METHODS: Forty-two patients with chronic nonallergic rhinitis were treated with Budesonide aqueous nasal spray (256 microg once daily intranasal) for 8 weeks. Bacteriological character was measured before and 8 weeks after treatment All the swab specimens were obtained from the inferior meatus, bacteriologic outcome was determined by general cultures. Nasal pH value was measured by using a probe sited under the inferior turbinate before and after treatment. Efficacy was evaluated by measurement of nasal symptom scores and sign scores before and 8 weeks after treatment. RESULTS: The bacterial growth was present in 37 of 42 cases (88%) before the treatment (group 1), including 53 aerobic bacteria. The bacterial growth was present in 38 of 42 cases (90.47%) 8 weeks after treatment (group 2), including 46 aerobic bacteria. There was no significant difference in the bacterial distribution between group 1 and group 2 (chi2 = 0.416, P > 0.05). Budesonide aqueous nasal spray reduced pH value from 7.90 +/- 0.39 to 7.70 +/- 0.23 (t = 2.72, P < 0.05). All the parameters of symptoms were improved after treatment, including nasal obstruction, nasal secretions, itchy feeling of the nose, closed rhinolalia and headache. CONCLUSIONS: Glucocorticoid aqueous nasal spray could be used safely for eight weeks and does not increase the risk of aerobes and fungi infection and reduce the pH in chronic nonallergic rhinitis. It is effective in relieving symptoms of patients with chronic nonallergic rhinitis.