CD38 Deficiency Protects Mouse Retinal Ganglion Cells Through Activating the NAD+/Sirt1 Pathway in Ischemia-Reperfusion and Optic Nerve Crush Models.

Purpose: The purpose of this study was to investigate the protective effect of CD38 deletion on retinal ganglion cells (RGCs) in a mouse retinal ischemia/reperfusion (I/R) model and an optic nerve crush (ONC) model, and to elucidate the underlying molecular mechanisms. Methods: Retinal I/R and ONC models were constructed in mice. PCR was used to identify the deletion of CD38 gene in mice, hematoxylin and eosin (H&E) staining was used to evaluate the changes in retinal morphology, and electroretinogram (ERG) was used to evaluate the changes in retinal function. The survival of RGCs and activation of retinal macroglia were evaluated by immunofluorescence staining. The expression of Sirt1, CD38, Ac-p65, Ac-p53, TNF-α, IL-1ß, and Caspase3 proteins in the retina was further evaluated by protein imprinting. Results: In retinal I/R and ONC models, CD38 deficiency reduced the loss of RGCs and activation of macroglia and protected the retinal function. CD38 deficiency increased the concentration of NAD+, reduced the degree of acetylation of NF-κB p65 and p53, and reduced expression of the downstream inflammatory cytokines TNFα, IL-1ß, and apoptotic protein Caspase3 in the retina in the ONC model. Intraperitoneal injection of the Sirt1 inhibitor EX-527 partially counteracted the effects of CD38 deficiency, suggesting that CD38 deficiency acts at least in part through the NAD+/Sirt1 pathway. Conclusions: CD38 plays an important role in the pathogenesis of retinal I/R and ONC injury. CD38 deletion protects RGCs by attenuating inflammatory responses and apoptosis through the NAD+/Sirt1 pathway.

Acupuncture for dyspnea and breathing physiology in chronic respiratory diseases: A systematic review and meta-analysis of randomized controlled trials.

Background: Dyspnea, a common symptom of chronic respiratory diseases (CRDs), is closely linked to higher levels of functional impairment and death, leading to significant societal and financial challenges. Despite numerous clinical trials and systematic reviews suggested the potential benefits of acupuncture for chronic obstructive pulmonary disease (COPD) and lung cancer, there is currently insufficient evidence to conclusively prove its effectiveness in alleviating dyspnea in patients with CRDs. Methods: To compile and evaluate the existing data on the effectiveness and safety of acupuncture for managing dyspnea in CRDs. Randomized controlled trials investigating acupuncture for the treatment of dyspnea in patients with CRDs, such as COPD, lung cancer, asthma, bronchiectasis, interstitial lung disease, chronic pulmonary heart disease and bronchitis, were searched and retrieved from five electronic databases in English or Chinese. Results: A total of 23 studies meeting the inclusion criteria were found in databases, covering various CRDs such as COPD, lung cancer, and asthma. A meta-analysis that compared acupuncture to a control group (which included no acupuncture and sham acupuncture) found significant advantages for acupuncture in reducing dyspnea severity (P = 0.0003), increasing 6MWD (P < 0.00001), improving quality of life measured by St. George's Respiratory Questionnaire (P = 0.03) and karnofsky performance status score (P < 0.00001). No significance was found in breathing physiology represented by FEV1 (P = 0.34) and FVC (P = 0.15). There was a comparable incidence of negative outcomes in both groups (P = 0.07). Results were consistent when compared to sham acupuncture. In addition, subgroup analyses were also consistent when different diseases or types of acupuncture were analyzed. Conclusions: Acupuncture may be an effective and safe non-pharmacological complementary intervention to relief dyspnea for patients with CRDs. Nevertheless, research with high quality and large sample sizes is needed for further investigation.

Progress and Challenges in Tumor Ferroptosis Treatment Strategies: A Comprehensive Review of Metal Complexes and Nanomedicine.

Ferroptosis is a new form of regulated cell death featuring iron-dependent lipid peroxides accumulation to kill tumor cells. A growing body of evidence has shown the potential of ferroptosis-based cancer therapy in eradicating refractory malignancies that are resistant to apoptosis-based conventional therapies. In recent years, studies have reported a number of ferroptosis inducers that can increase the vulnerability of tumor cells to ferroptosis by regulating ferroptosis-related signaling pathways. Encouraged by the rapid development of ferroptosis-driven cancer therapies, interdisciplinary fields that combine ferroptosis, pharmaceutical chemistry, and nanotechnology are focused. First, the prerequisites and metabolic pathways for ferroptosis are briefly introduced. Then, in detail emerging ferroptosis inducers designed to boost ferroptosis-induced tumor therapy, including metal complexes, metal-based nanoparticles, and metal-free nanoparticles are summarized. Subsequently, the application of synergistic strategies that combine ferroptosis with apoptosis and other regulated cell death for cancer therapy, with emphasis on the use of both cuproptosis and ferroptosis to induce redox dysregulation in tumor and intracellular bimetallic copper/iron metabolism disorders during tumor treatment is discussed. Finally, challenges associated with clinical translation and potential future directions for potentiating cancer ferroptosis therapies are highlighted.

Acupuncture for dyspnea and breathing physiology in chronic respiratory diseases: A protocol of a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD. METHODS: We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance. CONCLUSION: This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.

Diode laser transscleral cyclophotocoagulation causes intraocular collamer lens displacement in pseudophakic eye: a case report.

BACKGROUND: With the rapid development of intraocular collamer lens (ICL) operation, it is foreseeable that we will encounter a large number of glaucoma patients with ICL implantation history. However, our current understanding of the treatment of glaucoma patients with ICL is limited. Hence we report a rare case of refractory glaucoma after intraocular collamer lens and intraocular lens implantation in a patient who underwent unsuccessful transscleral cyclophotocoagulation, which led to intraocular collamer lens displacement, angle closure and uncontrolled intraocular pressure. CASE PRESENTATION: A 39-year-old woman presented with intractably elevated intraocular pressure in the right eye. Since her intraocular collamer lens implantation surgery in 2017, her intraocular pressure had remained over 40 mmHg while using 3 types of anti-glaucoma medications. The patient had a history of phacoemulsification and posterior chamber phakic intraocular lens implantation for complicated cataracts secondary to uveitis in 2006. On gonioscope examination, there were signs of pigment dispersion, and the anterior chamber angle was open. Ultrasound biomicroscopy examination showed contact and rubbing between the intraocular collamer lens and posterior surface of the iris. And typical advanced glaucomatous optic neuropathy and visual field defects were observed. Transscleral cyclophotocoagulation was performed to control the intraocular pressure and prevent further visual field loss. However, the intraocular collamer lens was displaced after transscleral cyclophotocoagulation, which resulted in formation of a shallow anterior chamber 1 week later, angle closure and loss of intraocular pressure control 1 month later, even though the maximum dose of anti-glaucoma medication was used. Finally, an Ahmed glaucoma valve was successfully implanted in her anterior chamber, and the glaucoma was controlled, as observed at the 10-month follow-up. CONCLUSIONS: Pigment dispersion is a common phenomenon after intraocular collamer lens implantation and may accelerate the progression of glaucoma. Transscleral cyclophotocoagulation should be carefully considered in glaucoma patients with elevated intraocular pressure after intraocular collamer lens implantation, given that transscleral cyclophotocoagulation may cause intraocular collamer lens displacement.

Effects of modulation on sodium and potassium channel currents by extremely low frequency electromagnetic fields stimulation on hippocampal CA1 pyramidal cells.

To investigate the effects of extremely low-frequency electromagnetic fields (ELF-EMFs) stimulation on sodium channel currents (INa), transient outward potassium channel currents (IA) and delayed rectifier potassium channel currents (IK) on hippocampal CA1 pyramidal neurons of young Sprague-Dawley rats. CA1 pyramidal neurons of rat hippocampal slices were subjected to ELF-EMFs stimulation with different frequencies (15 and 50 Hz), intensities (0.5, 1 and 2 mT) and durations (10, 20 and 30 min). The INa, IA and IK of neurons were recorded by a whole-cell patch-clamp method. ELF-EMFs stimulation enhanced INa densities, and depressed IA and IK densities. In detail, INa was more sensitive to the variation of intensities and frequencies of ELF-EMFs, whereas IA and IK were mainly affected by the variation of the duration of ELF-EMFs. ELF-EMFs stimulation altered activation and deactivation properties of INa, IA and IK. ELF-EMFs stimulation plays a role as a regulator rather than an inducer for ion channels. It might change the transition probability of ion channel opening or closing, and might also change the structure and function of the ion channel which need to be proved by the further technical method.

Role of the PGE2 receptor in ischemia-reperfusion injury of the rat retina.

Purpose: To investigate the function and expression of the PGE2 receptors EP1-4 in rat retinal ischemia-reperfusion (I/R) injury and to determine the regulatory role of resveratrol (RES) in this process. Methods: In vitro, we stimulated primary astrocytes extracted from the optic disc of rats with epidermal growth factor (EGF) and RES, and detected the location of EP1-4 expression with immunofluorescence. The expression of antiglial fibrillary acidic protein (GFAP), EGF receptor (EGFR), inducible NOS (iNOS), and EP1-4 in astrocytes was detected with western blotting. In vivo, we established an I/R injury model and RES treatment model with Sprague-Dawley rats. Changes in the thickness of the inner retina were observed with hematoxylin and eosin (H&E) staining. EP1-4 localization in the retina was observed with immunohistochemistry. The expression of COX-2, iNOS, and EP1-4 in the control and model groups was detected with western blotting. Results: In this study, immunofluorescence and immunohistochemistry showed that EP1-4 are expressed in astrocytes and the rat retina. EGF stimulation increased the expression of EGFR, iNOS, EP1, EP2, and EP4 in astrocytes. The expression of EP1-4 was statistically significantly increased on the third day after model induction, and EP1-4 expression decreased to normal levels on day 7. EGF and RES mediated the decrease in the expression of EP2. RES treatment significantly reduced retinal damage and RGC loss, as demonstrated by the relatively intact tissue structure on day 7 observed with H&E staining. Moreover, inflammation was associated with this I/R injury model, as demonstrated by the early induction of proinflammatory mediators, and this inflammation was significantly attenuated after RES treatment. Conclusions: These results indicate that the COX-2/PGE2/EPs pathway is involved in retinal damage and astrocyte inflammation. In addition, the results suggest that the neuroprotective effects of RES may be associated with decreased production of inflammatory mediators. These results suggest that the PGE2 receptor may be a key factor in the treatment of neurodegenerative diseases, and that RES may be used as a possible therapeutic strategy for glaucoma.

Identification of Steps in the Pathway of Arsenosugar Biosynthesis.

Arsenosugars are arsenic-containing ribosides that play a substantial role in arsenic biogeochemical cycles. Arsenosugars were identified more than 30 years ago, and yet their mechanism of biosynthesis remains unknown. In this study we report identification of the arsS gene from the cyanobacterium Synechocystis sp. PCC 6803 and show that it is involved in arsenosugar biosynthesis. In the Synechocystis sp. PCC 6803 ars operon, arsS is adjacent to the arsM gene that encodes an As(III) S-adenosylmethionine (SAM) methyltransferase. The gene product, ArsS, contains a characteristic CX3CX2C motif which is typical for the radical SAM superfamily. The function of ArsS was identified from a combination of arsS disruption in Synechocystis sp. PCC 6803 and heterologous expression of arsM and arsS in Escherichia coli. Both genes are necessary, indicating a multistep pathway of arsenosugar biosynthesis. In addition, we demonstrate that ArsS orthologs from three other freshwater cyanobacteria and one picocyanobacterium are involved in arsenosugar biosynthesis in those microbes. This study represents the identification of the first two steps in the pathway of arsenosugar biosynthesis. Our discovery expands the catalytic repertoire of the diverse radical SAM enzyme superfamily and provides a basis for studying the biogeochemistry of complex organoarsenicals.

Effectiveness of Traditional Chinese Medicine on chemo-radiotherapy induced leukaemia in patients with lung cancer: a Meta-analysis.

OBJECTIVE: To assess the curative effect of Traditional Chinese Medicine (TCM) on leukopenia induced by chemo-radiotherapy in patients with lung cancer. METHODS: A comprehensive electronic search in Medline, Embase, the Cochrane Libary database, China National Knowledge Infrastructure Database (CNKI) and Wanfang Database was conducted up to July 2017. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Eleven studies with a total of 957 patients were included in this meta-analysis. RESULTS: The effectiveness in TCM group was higher than control group [RR = 1.60, 95% CI (1.38, 1.85), P < 0.000 01]. Compare with Western Medicine group, the effectiveness has no significant difference [RR = 0.96, 95% CI (0.82, 1.12), P = 0.57]. The ineffective rate in test group was lower than the control group [RR = 0.30, 95% CI (0.21, 0.42), P < 0.000 01]. CONCLUSION: By meta-regression it was suggested that TCM has curative effect on leukopenia induced by chemo-radiotherapy in patients with lung cancer, but by the influence of number and quality of researches, publication bias, more evidence from high quality studies, and larger cohorts for observational trials are needed.