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.

Exploring the Effect of Arsenic-Containing Hydrocarbon on the Bidirectional Synaptic Plasticity of the Dorsal Hippocampus.

Arsenic-containing hydrocarbons (AsHCs) are common in marine organisms. However, there is little research on their effects on the central nervous system's advanced activities, such as cognition. Bidirectional synaptic plasticity dynamically regulates cognition through the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the effects of AsHCs on bidirectional synaptic plasticity and the underlying molecular mechanisms remain unexplored. This study provides the first evidence that 15 µg As L-1 AsHC 360 enhances bidirectional synaptic plasticity, occurring during the maintenance phase rather than the baseline phase. Further calcium gradient experiments hypothesize that AsHC 360 may enhance bidirectional synaptic plasticity by affecting calcium ion levels. The enhancement of bidirectional synaptic plasticity by 15 µg As L-1 AsHC 360 holds significant implications in improving cognitive function, treating neuro-psychiatric disorders, promoting neural recovery, and enhancing brain adaptability.

Speciation of arsenic in milk from cows fed seaweed.

BACKGROUND: Including seaweed in cattle feed has gained increased interest, but it is important to take into account that the concentration of toxic metals, especially arsenic, is high in seaweed. This study investigated the arsenic species in milk from seaweed-fed cows. RESULTS: Total arsenic in milk of control diets (9.3 ± 1.0 µg As kg-1, n = 4, dry mass) was significantly higher than seaweed-based diet (high-seaweed diet: 7.8 ± 0.4 µg As kg-1, P < 0.05, n = 4, dry mass; low-seaweed diet: 6.2 ± 1.0 µg As kg-1, P < 0.01, n = 4, dry mass). Arsenic speciation showed that the main species present were arsenobetaine (AB) and arsenate (As(V)) (37% and 24% of the total arsenic, respectively). Trace amounts of dimethylarsinic acid (DMA) and arsenocholine (AC) have also been detected in milk. Apart from arsenate being significantly lower (P < 0.001) in milk from seaweed-fed cows than in milk from the control group, other arsenic species showed no significant differences between groups. CONCLUSION: The lower total arsenic and arsenate in seaweed diet groups indicates a possible competition of uptake between arsenate and phosphate, and the presence of AC indicates that a reduction of AB occurred in the digestive tract. Feeding a seaweed blend (91% Ascophyllum nodosum and 9% Laminaria digitata) does not raise As-related safety concerns for milk. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

AsHC 360 Exposure Influence on Epileptiform Discharges in Hippocampus of Infantile Male Rats In Vitro.

Arsenic-containing hydrocarbons (AsHCs) are typical arsenolipids found in various marine organisms. They can penetrate the blood-brain barrier, specifically affecting synaptic plasticity and the learning and memory ability of hippocampal neurons. Temporal lobe epilepsy often occurs in the hippocampus. Thus, the possible influence of AsHCs exposure to temporal lobe epilepsy garnered attention. The present study investigated the effects of epileptiform discharges (EDs) signals introduced by low-magnesium ACSF in the hippocampus of infantile male rats in vitro, using electrophysiological techniques with multi-electrode arrays under AsHC 360 exposure. In our study of the effects of AsHC 360 on EDs signals, we found that inter-ictal discharges (IIDs) were not significantly impacted. When AsHC 360 was removed, any minor effects observed were reversed. However, when we examined the impact of AsHC 360 on ictal discharges (IDs), distinct patterns emerged based on the concentration levels. For low-concentration groups (5, 20, 60 µg As L-1), both the frequency and duration effects on IDs returned to normal post-elimination of AsHC 360. However, this recovery was not evident for concentrations of 100 µg As L-1 or higher. IDs were only observed in EDs signals during exposures to AsHC 360 concentrations up to 60 µg As L-1. In these conditions, ID frequencies significantly enhanced with the increased of AsHC 360 concentration. At high concentrations of AsHC 360 (≥100 µg As L-1), the transition from IIDs or pre-ictal discharges (PIDs) to IDs was notably inhibited. Additional study on co-exposure of AsHC 360 (100 µg As L-1) and agonist (10 nM (S)-(-)-Bay-K-8644) indicated that the regulation of EDs signals under AsHC 360 exposure could be due to directly interference with the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) expression which influences the binding of excitatory glutamate neurotransmitter to AMPAR. The results suggest that EDs activities in the hippocampus of infantile Sprague Dawley rats are concentration-dependent on AsHC 360 exposure. Thus, it provides a basis for the seafood intake with AsHCs for epileptic patients and those with potential seizures.

Arsenolipids reduce butyrate levels and influence human gut microbiota in a donor-dependent way.

Arsenolipids are organic arsenic species with variable toxicity. Accurate assessment of the risks derived from arsenic-contaminated seafood intake requires studying the interplay between arsenolipids and the human gut microbiota. This research used the in vitro mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) to assess the effect of defined chemical standards of arsenolipids (AsFA 362 and AsHC 332) on a simulated healthy human gut microbiota (n = 4). Microbial-derived metabolites were quantified by gas chromatography and microbiota structure was characterized by 16S rRNA gene sequencing. A specific reduction in butyrate production (control=5.28 ± 0.3 mM; AsFAs=4.56 ± 0.4 mM; AsHC 332=4.4 ±â€¯0.6 mM, n = 4 donors), concomitant with a reduction in the abundance of Lachnospiraceae UCG-004 group and the Faecalibacterium genus was observed, albeit in a donor-dependent manner. Furthermore, an increase in Escherichia/Shigella, Proteobacteria and Fusobacterium abundance was observed after arsenolipid treatments, depending on individual microbiota background. These alterations in microbial functionality and microbial community structure suggest a detrimental effect of arsenolipids intake towards the commensal gut microbiome, and consequently, on human health.

Gut microbiota metabolize arsenolipids in a donor dependent way.

Understanding the interplay between the gut microbiome and arsenolipids can help us manage the potential health risk of consuming seafood, but little is known about the bioconversion fate of arsenolipids in the gastrointestinal tract. We use an in vitro mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) to mimic the digestive tract of four healthy donors during exposure to two arsenolipids (an arsenic fatty acid AsFA 362 or an arsenic hydrocarbon AsHC 332). The metabolites were analyzed by HPLC-mass spectrometry. The human gut bacteria accumulated arsenolipids in a donor-dependent way, with higher retention of AsHC 332. Colonic microbiota partly transformed both arsenolipids to their thioxo analogs, while AsFA 362 was additionally transformed into arsenic-containing fatty esters, arsenic-containing fatty alcohols, and arsenic-containing sterols. There was no significant difference in water-soluble arsenicals between arsenolipid treatments. The study shows that arsenolipids can be quickly biotransformed into several lipid-soluble arsenicals of unknown toxicity, which cannot be excluded when considering potential implications on human health.

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.

Salivary and Gut Microbiomes Play a Significant Role in in Vitro Oral Bioaccessibility, Biotransformation, and Intestinal Absorption of Arsenic from Food.

The release of a toxicant from a food matrix during the gastrointestinal digestion is a crucial determinant of the toxicant's oral bioavailability. We present a modified setup of the human simulator of the gut microbial ecosystem (SHIME), with four sequential gastrointestinal reactors (oral, stomach, small intestine, and colon), including the salivary and colonic microbiomes. Naturally arsenic-containing rice, mussels, and nori seaweed were digested in the presence of microorganisms and in vitro oral bioaccessibility, bioavailability, and metabolism of arsenic species were evaluated following analysis by using HPLC/mass spectrometry. When food matrices were digested with salivary bacteria, the soluble arsenic in the gastric digestion stage increased for mussel and nori samples, but no coincidence impact was found in the small intestinal and colonic digestion stages. However, the simulated small intestinal absorption of arsenic was increased in all food matrices (1.2-2.7 fold higher) following digestion with salivary microorganisms. No significant transformation of the arsenic species occurred except for the arsenosugars present in mussels and nori. In those samples, conversions between the oxo arsenosugars were observed in the small intestinal digestion stage whereupon the thioxo analogs became major metabolites. These results expand our knowledge on the likely metabolism and oral bioavailabiltiy of arsenic during human digestion, and provide valuable information for future risk assessments of dietary arsenic.

[Determination of 20 Trace Elements in the Blood Collection Tubes with ICP-MS].

To investigate the contamination of blood collection tubes, 20 trace elements (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sn, Sb, Ba, W, Hg, Tl, Pb) in 13 different types of blood collection tube were studied with ICP-MS method. The lixivium of H(2)O and 10% HNO(3) were measured with ICP-MS, and then the contamination coming from the blood collection tube is specified. According to the concentration range of human blood, plasma and serum from recently published literature, this report presents a detailed analysis of capable trace elements for each blood collection tube. The results showed that, tube No.1 is capable to analyze 18 trace elements in the human serum; tube No.6 is capable to analyze 15 trace elements in the human plasma; tube No. 13 is capable to analyze 17 trace elements in the human blood. But we still should be aware that, the elements Sb and W in tube No.1, the elements V, Cr, Ni, and Sb in tube No.6, and the elements Al, Sb and W in tube No.13, are in the same magnitude of the normal trace element concentration range in the human serum, plasma and blood. They might affect the testing results. The serum collected from the same volunteer by tube No.1 and tube No.3 were compared here, the results show that, almost each trace element concentration of human serum from tube No.1 is lower than from tube No.3, especially for elements Al, V, Cr, Mn, As, Sn, and Sb. The results indicate that the blood collection tubes show great impact on determination of trace element.

Rapid detection of SARS-CoV-2 spike protein using a magnetic-assisted electrochemical biosensor based on functionalized CoFe2O4 magnetic nanomaterials.

The outbreak of novel coronavirus pneumonia (COVID-19) in 2019 has garnered widespread attention. The virus exhibits high contagiousness, and in certain cases, it can lead to recurrent infections. Therefore, it is imperative to develop portable, sensitive, and accurate sensors to promptly detect infected individuals, control the virus's transmission, and determine suitable treatment strategies. In this study, we proposed a magnetically-assisted method employing CFO@CS-Au MNP as the substrate material, which was functionalized with human angiotensin-converting enzyme (ACE2) for efficient capture of SARS-CoV-2 spike protein in solution. Subsequently, the captured protein was sensitively detected through differential pulse voltammetry (DPV) electrical analysis. The linear detection range of the labeled GCE/MNP/GA/ACE2/BSA electrochemical sensor is from 1 pg/mL to 10 µg/mL, with a minimum detection limit of 0.15 pg/mL. Furthermore, the fabricated GCE/MNP/GA/ACE2/BSA sensor achieved satisfactory recoveries of SARS-CoV-2 spike protein in saliva and nasal swab samples within 10 min. These results indicate that this magnetically-assisted biosensor has established a solid foundation for the swift on-site detection of COVID-19.

Dually-amplified electrochemical aptasensor based on the self-linking AuPt nanoflowers for ultrasensitive determination of hemagglutinin.

BACKGROUND: Influenza virus can spread from person to person and cause epidemics. Therefore, rapid and sensitive diagnosis of virus is essential in controlling influenza outbreaks. Conventional virus diagnostic techniques are time-consuming, labor-intensive and requires large instruments. In this work, a sandwich electrochemical assay by a pair of aptamers was developed for ultrasensitive determination of hemagglutinin (HA) protein, which is one of the two surface glycoproteins of influenza A (H1N1) virus, using dual signal amplification techniques. RESULTS: HA was captured and magnetically separated by Fe3O4@SiO2-NH2@Au attached to aptamer 1 (Apt1), creating a sandwich structure with AuPt nanoflowers (AuPtNFs) connected to aptamer 2 (Apt2). Herein, AuPtNFs could catalyze H2O2/hydroquinone (HQ) to generate 1,4-benzoquinone (BQ), and achieved amplification of electrochemical signal detection through differential pulse voltammetry (DPV). The constructed aptasensor expressed a wide linear range (10 pg/mL-100 ng/mL) with limit of detection (LOD) of 2.4 pg/mL. Moreover, a novel strategy for dual signal amplification was developed to further enhance sensitivity. The innovative electrochemical aptasensor could achieve secondary amplification of the detection signal with LOD of 0.3 pg/mL and linear concentration range from 0.5 pg/mL to 100 ng/mL. The secondary amplification could be achieved only through the self-linking process, which allowed for the retention of numerous AuPtNFs by simple complementary base pairing to connect more AuPtNFs onto the above-mentioned sandwich structure. SIGNIFICANCE: Overall, the constructed aptasensor exhibited favorable sensitivity and accuracy, indicating the potential expanded application for the clinical detection of numerous viruses.

Effectiveness and safety of acupuncture as an adjunctive therapy for chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. METHODS: This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40-80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. RESULTS: Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. CONCLUSIONS: Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects.

Noninvasive Light Flicker Stimulation Promotes Optic Nerve Regeneration by Activating Microglia and Enhancing Neural Plasticity in Zebrafish.

Purpose: Forty-hertz light flicker stimulation has been proven to reduce neurodegeneration, but its effect on optic nerve regeneration is unclear. This study explores the effect of 40-Hz light flicker in promoting optic nerve regeneration in zebrafish and investigates the underlying mechanisms. Methods: Wild-type and mpeg1:EGFP zebrafish were used to establish a model of optic nerve crush. Biocytin tracing and hematoxylin and eosin staining were employed to observe whether 40-Hz light flicker promotes regeneration of retinal ganglion cell axons and dendrites. Optomotor and optokinetic responses were evaluated to assess recovery of visual function. Immunofluorescence staining of mpeg1:EGFP zebrafish was performed to observe changes in microglia. Differentially expressed genes that promote optic nerve regeneration following 40-Hz light flicker stimulation were identified and validated through RNA-sequencing analysis and quantitative real-time PCR (qRT-PCR). Results: Zebrafish exhibited spontaneous optic nerve regeneration after optic nerve injury and restored visual function. We observed that 40-Hz light flicker significantly activated microglia following optic nerve injury and promoted regeneration of retinal ganglion cell axons and dendrites, as well as recovery of visual function. Transcriptomics and qRT-PCR analyses revealed that 40-Hz light flicker increased the expression of genes associated with neuronal plasticity, including bdnf, npas4a, fosab, fosb, egr4, and ier2a. Conclusions: To our knowledge, this study is the first to demonstrate that 40-Hz light flicker stimulation promotes regeneration of retinal ganglion cell axons and dendrites and recovery of visual function in zebrafish, which is associated with microglial activation and enhancement of neural plasticity.

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.

Efficacy and cerebral mechanisms of acupuncture for chronic obstructive pulmonary disease: study protocol for a multicenter, randomized controlled neuroimaging trial.

Introduction: Although acupuncture is recommended by chronic obstructive pulmonary disease (COPD) treatment guidelines owing to its effects on dyspnea, the underlying neurobiological mechanisms of these effects remain unclear. This study aims to evaluate the efficacy of acupuncture in patients with stable COPD and explore the possible involvement of specific brain regions. Methods: This is a prospective, multicenter, single-blind, randomized controlled trial. A total of 90 participants will be recruited from three centers and will be randomly assigned in a 1:1 ratio to undergo acupuncture at acupoints on the disease-affected meridian (DAM) or non-acupoints on the non-affected meridian (NAM), in addition to routine pharmacological treatments. All participants will undergo 30 min of acupuncture three times a week for 8 weeks and will be followed up for 12 months. The primary outcome will be the severity of dyspnea, as measured using the Borg Dyspnea Scale and a visual analog scale at rest and after exercise. The secondary outcomes will include the multidimensional profile of dyspnea using Dyspnea-12, the modified Medical Research Council Dyspnea Scale, and the COPD assessment test; quality of life assessments using St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale; and additional measurements of exacerbation frequency, pulmonary function, and the 6-min walking distance. Magnetic resonance imaging (MRI) will be performed before and after exercise to explore the potential neurobiological mechanisms of exertional dyspnea. Anxiety and depression will be measured and analyzed for their correlation with the activation of specific brain areas involved in dyspnea. Discussion: This randomized controlled trial aims to use a multidimensional evaluation of the efficacy of acupuncture in relieving dyspnea in patients with COPD in terms of emotion and quality of life and explore the neurobiological mechanisms underlying the effects of acupuncture on dyspnea from an imaging perspective. It is expected to provide strong evidence to support the use of acupuncture in relieving dyspnea in patients with COPD and those with aother diseases involving dyspnea. Additionally, it provides novel insights into the central mechanisms of acupuncture intervention and dyspnea. Trial registration: Chinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2300071725.

Values of macular ganglion cell-inner plexiform layer and 10-2 visual field measurements in detecting and evaluating glaucoma.

AIM: To assess the performance of macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and 10-2 visual field (VF) parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma. METHODS: Totally 127 eyes from 89 participants (36 eyes of 19 healthy participants, 45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients) were included. The relationships between the optical coherence tomography (OCT)-derived parameters and VF sensitivity were determined. Patients with early glaucoma were divided into eyes with or without central 10° of the VF damages (CVFDs), and the diagnostic performances of OCT-derived parameters were assessed. RESULTS: In early glaucoma, the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation (PSD; with average mGCIPLT: ß=-0.046, 95%CI, -0.067 to -0.024, P<0.001). In advanced glaucoma, the mGCIPLT was related to the 24-2 VF mean deviation (MD; with average mGCIPLT: ß=0.397, 95%CI, 0.199 to 0.595, P<0.001), 10-2 VF MD (with average mGCIPLT: ß=0.762, 95%CI, 0.485 to 1.038, P<0.001) and 24-2 VF PSD (with average mGCIPLT: ß=0.244, 95%CI, 0.124 to 0.364, P<0.001). Except for the minimum and superotemporal mGCIPLT, the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs. The area under the curve (AUC) of the average mGCIPLT (AUC=0.949, 95%CI, 0.868 to 0.982) was greater than that of the average circumpapillary retinal nerve fiber layer thickness (cpRNFLT; AUC=0.827, 95%CI, 0.674 to 0.918) and rim area (AUC=0.799, 95%CI, 0.610 to 0.907) in early glaucomatous eyes with CVFDs versus normal eyes. CONCLUSION: The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF, cpRNFLT and ONH parameters, especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

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.