Impacts of air pollution and meteorological conditions on dry eye disease among residents in a northeastern Chinese metropolis: a six-year crossover study in a cold region.

The purpose of this study is to explore the associations among dry eye disease (DED), air pollution, and meteorological conditions in the cold region of a northeastern Chinese metropolis (i.e., Changchun). Data on ambient air pollutants and meteorological parameters as well as diagnosed DED outpatients during 2015-2021 were collected. The associations between DED and environmental factors were analysed at multiple time scales using various statistical methods (i.e., correlation, regression and machine learning). Among the 10,809 DED patients (21,617 eyes) studied, 64.60% were female and 35.40% were male. A higher frequency of DED was observed in March and April, followed by January, August and October. Individual and multiple factor models showed the positive importance of particles with aerodynamic diameters <10 µm (PM10), carbon monoxide (CO), and ozone (O3) among normal air pollutants and air pressure (AP), air temperature (AT) and wind speed (WS) among normal meteorological parameters. Air pollutants (PM10, nitrogen dioxide: NO2) and meteorological parameters (AT, AP) have combined impacts on DED occurrence. For the first time, we further explored the associations of detailed components of atmospheric particles and DED, suggesting potential emission sources, including spring dust from bare soil and roads and precursor pollutants of summer O3 formation from vehicles and industry in Northeast China. Our results revealed the quantitative associations among air pollutants, meteorological conditions and DED outpatients in cold regions, highlighting the importance of coordinated policies in air pollution control and climate change mitigation.

Rejection of Acellular Porcine Corneal Stroma Transplantation During Coronavirus Disease 2019 Pandemic.

ABSTRACT: To report 2 successfully managed cases of graft rejection with acellular porcine corneal stroma (APCS) transplantation in patients with fungal corneal ulcer. Two patients were diagnosed with fungal corneal ulcer and received APCS transplantation. Graft rejection developed due to the lost follow-up during the period of coronavirus disease 2019 outbreak. Amniotic membranes transplantation and cauterization of neovascularization was performed, respectively. The graft failure resolved successfully after the procedure. To the best of our knowledge, amniotic membranes transplantation and cauterization of new vessels are the firstly reported in treating APCS graft failure. Amniotic membranes transplantation or cauterization of neovascularization appear to be a safe and costeffective method for treating graft failure.

Mechanistic insights into the amelioration effects of lipopolysaccharide-induced acute lung injury by baicalein: An integrated systems pharmacology study and experimental validation.

BACKGROUND: Acute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. OBJECTIVES: In this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. METHODS: Forty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FINDINGS: The results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. CONCLUSION: Baicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.

The Effect of Erector Spinae Plane Blockade on Prevention of Postherpetic Neuralgia in Elderly Patients: A Randomized Double-blind Placebo-controlled Trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common chronic complication following the onset of herpes zoster (HZ). Both the incidence of HZ and the proportion of patients with HZ who develop PHN rise with age. Ultrasound-guided erector spinae plane blockade (ESPB) has been reported to relieve neuropathic pain and PHN in elderly patients, but no randomized controlled trials have been conducted regarding the effect of ESPB on elderly patients with HZ in the acute or subacute phases. OBJECTIVES: To evaluate the effect of repeated ESPB on the occurrence of PHN in elderly patients with acute or  subacute HZ. STUDY DESIGN: A randomized double blind placebo-controlled trial with 2 parallel groups. SETTING: A university hospital in China. METHODS: Patients diagnosed with acute or subacute HZ were randomized to receive either ultrasound-guided ESPB (the ESPB group) or placebo subcutaneous injection (the control group) every 24 hours for 3 days. Patients were followed up at 12 weeks after the final treatment. The primary end point was the incidence of PHN at 12 weeks. RESULTS: A total of 52 patients were enrolled and randomized; 50 completed 12 weeks of follow-up. The incidence of PHN at 12 weeks was significantly lower in the ESPB group (15.4% [4/26]) than in the control group (41.7% [10/24]); relative risk 0.37, 95% confidence interval 0.13-1.02, P = 0.039. At 12 weeks, the VAS scores at rest and the total scores from the Short-Form McGill Pain Questionnaire-2 were significantly decreased in the ESPB group (P = 0.046 and P = 0.001, respectively). The incidence of neuropathic pain, sleep disturbance, and anxiety/depression were significantly reduced in the ESPB group (P = 0.002, P = 0.002, and P = 0.025, respectively). Patients using tramadol and hypnotics as well as total complications with oral medicines were remarkably decreased in the ESPB group (P = 0.008, P = 0.002, and P = 0.042 respectively). The adverse events during or after the procedure were comparable between the groups. LIMITATIONS: This trial was carried out in a single center with a 12-week follow-up. Nearly 8% of patients in the control group were lost to follow-up. CONCLUSIONS: For elderly patients suffering acute or subacute HZ, ESPB reduces the incidence of PHN at 12 weeks after treatment; it also decreases the occurrence of neuropathic pain, sleep disturbance, and anxiety/depression.

Air pollution and meteorological conditions significantly contribute to the worsening of allergic conjunctivitis: a regional 20-city, 5-year study in Northeast China.

This study is the first to explore the potential associations among allergic conjunctivitis (AC), air pollution, and meteorological conditions in Northeast China. Data of meteorology, ambient atmospheric pollutants, and the incidence of allergic conjunctivitis (IAC) in prefecture-level cities between the years 2014 and 2018 are analyzed. The results show an increasing trend in the AC of average growth rate per annum 7.6%, with the highest incidence in the provincial capitals. The IAC is positively correlated with atmospheric pollutants (i.e., PM2.5, PM10, CO, SO2, NO2, and O3) and meteorological factors (i.e., air temperature and wind speed), but negatively correlated with relative humidity. These results suggest that the IAC is directly proportional to pollution level and climatic conditions, and also the precedence of air pollution. We have further obtained the threshold values of atmospheric pollutants concentration and meteorological factors, a turning point above which more AC may be induced. Compared with the air quality standard advised by China and the World Health Organization (WHO), both thresholds of PM10 (70 µg m-3) and PM2.5 (45 µg m-3) are higher than current standards and pose a less environmental risk for the IAC. SO2 threshold (23 µg m-3) is comparable to the WHO standard and significantly lower than that of China's, indicating greater environmental risks in China. Both thresholds of NO2 (27 µg m-3) and O3 (88 µg m-3) are below current standards, indicating that they are major environmental risk factors for the IAC. Our findings highlight the importance of atmospheric environmental protection and reference for health-based amendment.

Use of Intense Pulsed Light to Mitigate Meibomian Gland Dysfunction for Dry Eye Disease.

Dry Eye Disease (DED) is a common ocular condition that needs prompt diagnosis and careful treatment interventions. If left untreated, it can lead to numerous sight-threatening complications, including ulceration of the cornea, blepharitis, alterations of the tear film, conjunctivitis, and in severe cases, may lead to scarring, thinning, and even perforation of the cornea. Intense pulsed light (IPL) is a non-laser high-intensity light source that has shown to play a valuable role in dry eye disease. Recent evidence from various research works has shown that IPL modifies the mechanism of meibomian gland dysfunction (MGD), which helps to relieve the symptoms of DED. In this review, we demonstrated the mechanism of action of IPL, including its benefits on DED. The emerging evidence shows that the role of IPL in DED is novel and therapeutic. These results direct us to conclude that IPL is a potentially beneficial tool and essential future therapy for dry eye disease. Advances in the treatment of DED will lead to a better quality of life. However, tools to recognize potentially severe side effects of DED earlier in order to treat or prevent them must be developed.

NONRATT021972 long-noncoding RNA: A promising lncRNA in diabetes-related diseases.

Diabetes mellitus (DM) is a principal health problem with increasing incidence worldwide. It can be associated with various systemic diseases. Long non-coding RNA (lncRNA), a member of non-coding RNA has been newly linked with various human diseases. Recent evidence from animal experiments has shown that the incidence and development of type 2 diabetes are contributed by the atypical expression of lncRNA in which the biomarker with capable clinical potential was lncRNA NONRATT021972. In this review, we demonstrated the numerous functions of NONRATT021972 in different diabetes-related diseases including diabetic neuropathy, diabetic cardiac autonomic neuropathy, myocardial ischemia, and hepatic glucokinase dysfunction. The emerging evidence shows that the role of NONRATT021972 in diabetic-related disease is novel and therapeutic. These results direct us to conclude that NONRATT021972 is a potential diagnostic and future targeted therapy for diabetes-associated diseases.

Circular RNAs: Novel Promising Biomarkers in Ocular Diseases.

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs produced by back-splicing. They are found to be expressed in eukaryotic cells and play certain roles in various cellular functions, including fibrosis, cell proliferation, differentiation, apoptosis and angiogenesis. Dysregulated circRNAs are found in several human disorders including, malignancy, vascular, inflammatory as well as nervous diseases. Although, increasing evidence suggests that circRNAs may also contribute in different ocular diseases, the outline of circRNAs in ocular diseases remains obscure. In this review we consider the current state of knowledge regarding the potential role and underlying mechanism of circRNAs in ocular diseases including pterygium, age-related cataract, glaucoma, diabetic retinopathy, retinoblastoma, retinal vascular dysfunction and hyperhomocysteinemia induced ocular diseases, emphasizing that circRNAs could be promising biomarkers for the diagnosis and prognosis evaluation. Future circRNAs-targeted intervention may become a novel therapeutic tool for the treatment of ocular diseases.

MALAT1 as a Diagnostic and Therapeutic Target in Diabetes-Related Complications: A Promising Long-Noncoding RNA.

Diabetes mellitus is a global issue with increasing incidence rate worldwide. In an uncontrolled case, it can advance to various organ-related complications leading to an increase in morbidity and mortality. Long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to be a fairly novel lncRNA that is relevant to diabetes and its role in diabetic-related diseases initiation and progression have long been a subject of attention to many scholars. The expression of MALAT1 is elevated in different diabetic-related diseases. In this review, we demonstrate the various functions of MALAT1 in the different diabetes-related complications including ischemic reperfusion injury, retinopathy, cataract, atherosclerosis, cardiomyopathy, non-alcoholic steatohepatitis, gastroparesis, kidney disease, and gestational diabetes. The emerging evidence showed that the role of MALAT1 in diabetic-related complications is both pro-inflammatory and apoptosis in different cell types. These results concluded that MALAT1 is a potential diagnostic and future targeted therapy for diabetes-associated complications.

The Effects of Lysimachia christinae Hance Extract Fractions on Endothelium-Dependent Vasodilatation.

BACKGROUND: Endothelium-dependent dilatation is a predictor for vascular function. NADPH oxidase-derived O2- can inactivate nitric oxide and induce vascular injury. METHOD: The crude ethanolic extract of Lysimachia christinae Hance were separated out 4 fractions of different olarities by petroleum ether, ethyl acetate, n-butanol (NB), and aqueous. The endothelial integrity was appraised by vascular tension measurement. Dihydroethidium was utilized to observe the vascular reactive oxygen species (ROS) production. Western-blot was adopted to detect protein expression. RESULTS: Among the 4 fractions of L. christinae Hance, the NB fraction showed the most potent capacity of promoting endothelium-dependent vascular relaxation and inhibiting ROS formation in aortic rings, which were likely attributed by suppressing the expression of NAD(P)H oxidase subunit (gp91phox, p47phox, and p67phox) and enhancing the phosphorylation of endothelial NOS in vascular tone. CONCLUSIONS: These results suggest that the NB fraction possess the strongest vascular pharmacological activities among the crude ethanolic extract of L. christinae Hance, which may help us for purifying bioactive constituents and discovering new drugs from this herb in future.

Anti-BCMA immunotoxins produce durable complete remissions in two mouse myeloma models.

Multiple myeloma (MM) is a B cell malignancy for which new treatments are urgently needed. The B cell maturation antigen (BCMA) is a lineage-restricted differentiation protein highly expressed on myeloma. Recombinant immunotoxins (RITs) are proteins composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. We previously treated H929 myeloma s.c. tumors with anti-BCMA immunotoxins, very active on killing cultured cells, and observed tumor growth inhibition but not complete tumor responses. To determine if immunotoxins were more active against cells growing in the bone marrow (BM), the normal location of myeloma cells, we developed a BM mouse model that is more relevant to human disease. H929 cells were transfected with luciferase and GFP, enriched by flow, recycled through the BM of a mouse, and injected IV into nonobese diabetic scid γ mice (NSG) mice. A second myeloma mouse model used the MM.1S-GFP-luc cell line. Mice were treated IV with immunotoxins, and the tumor burden was assessed using bioluminescence imaging. We achieved complete durable remissions when treating mice with H929-GFP-luc cells with anti-BCMA RITs both leptomycin B-75 (LMB-75) [anti-BCMA-disulfide-stabilized (ds)-Fv-PE24] (where PE represents Pseudomonas exotoxin A) or LMB-70 (anti-BCMA-Fab-PE24) given every other day for 5-d (QOD×5) doses beginning on day 4 or day 8. Mice were disease free at 3 months; untreated mice became moribund around day 40. We also achieved long-term responses using the MM.1S-GFP-luc myeloma cell line. Treatment with an 1.5 mg/kg LMB-75 QOD×5 anti-BCMA RIT beginning on day 4 caused the complete disappearance of tumors for 80 days. To summarize, LMB-75 and LMB-70, our anti-BCMA RITs, induced complete durable responses in two myeloma models.

Interplay between reversible phosphorylation and irreversible ADP-ribosylation of eukaryotic translation elongation factor 2.

The functionality of eukaryotic translation elongation factor 2 (eEF2) is modulated by phosphorylation, eEF2 is simultaneously the molecular target of ADP-ribosylating toxins. We analyzed the interplay between phosphorylation and diphthamide-dependent ADP-ribosylation. Phosphorylation does not require diphthamide, eEF2 without it still becomes phosphorylated. ADP-ribosylation not only modifies the H715 diphthamide but also inhibits phosphorylation of S595 located in proximity to H715, and stimulates phosphorylation of T56. S595 can be phosphorylated by CDK2 and CDK1 which affects EEF2K-mediated T56-phosphorylation. Thus, ADP-ribosylation and S595-phosphorylation by kinases occur within the same vicinity and both trigger T56-phosphorylation. Diphthamide is surface-accessible permitting access to ADP-ribosylating enzymes, the adjacent S595 side chain extends into the interior. This orientation is incompatible with phosphorylation, neither allowing kinase access nor phosphate attachment. S595 phosphorylation must therefore be accompanied by structural alterations affecting the interface to ADP-ribosylating toxins. In agreement with that, replacement of S595 with Ala, Glu or Asp prevents ADP-ribosylation. Phosphorylation (starvation) as well as ADP-ribosylation (toxins) inhibit protein synthesis, both affect the S595/H715 region of eEF2, both trigger T57-phosphorylation eliciting similar transcriptional responses. Phosphorylation is short lived while ADP-ribosylation is stable. Thus, phosphorylation of the S595/H715 'modifier region' triggers transient interruption of translation while ADP-ribosylation arrests irreversibly.

Curcumin protects against diabetic cardiomyopathy by promoting autophagy and alleviating apoptosis.

The effects of curcumin on regulating cardiac apoptosis and autophagy were analyzed in diabetic models both in vivo and in vitro. In vivo, experimental diabetes was induced in mice by low-dose STZ injection combined with a high-fat diet. In vitro, cultured H9c2 cardiomyoblasts were exposed to high d-glucose concentrations combined with palmitate. Our results showed that apoptosis was increased and autophagy was suppressed in the hearts of diabetic mice, which was ameliorated by curcumin treatment, ultimately improving cardiac function. Moreover, the inhibition of autophagy exacerbated apoptotic death in cardiac cells under diabetic condition. Curcumin activated AMPK and JNK1, which phosphorylated Bcl-2 and Bim and subsequently disrupted their interactions with Beclin1, thereby promoting autophagy and alleviating apoptosis respectively. In addition, AMPK-mediated inhibition of mTORC1 pathway likely played a role in regulating autophagy by curcumin under diabetic condition. Our study suggests that curcumin protects against diabetic cardiomyopathy by modulating the crosstalk between autophagic and apoptotic machinery. Modulation of autophagy may be an effective strategy for the treatment of cardiovascular diseases associated with diabetes.

The Nrf2 Signaling in Retinal Ganglion Cells under Oxidative Stress in Ocular Neurodegenerative Diseases.

Retinal ganglion cells (RGCs) are one of the important cell types affected in many ocular neurodegenerative diseases. Oxidative stress is considered to be involved in retinal RGCs death in ocular neurodegenerative diseases. More and more attention has been focused on studying the agents that may have neuroprotective effects. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key nuclear transcription factor for the systemic antioxidant defense system. This review elucidates the underlying mechanism of the Nrf2-mediated neuroprotective effects on RGCs in ocular neurodegenerative diseases, such as diabetic retinopathy and retinal ischemia-reperfusion injury. Several Nrf2 inducers that shield RGCs from oxidative stress-induced neurodegeneration via regulating Nrf2 signaling are discussed.

HOXA11 antisense long noncoding RNA (HOXA11-AS): A promising lncRNA in human cancers.

The cancers are the leading cause of disease-related deaths worldwide with a high risk of morbidity and mortality. Long noncoding RNAs (lncRNAs) play a critical role in a wide range of biological processes, including tumorigenesis. HOXA11-AS (NCRNA00076), the antisense strands of HOXA11 gene, was initially revealed in a mouse embryonic cDNA library in 2009 and it was a fairly novel lncRNA. This review summarized the advanced research progression concerning the expression and role of HOXA11-AS in different human malignancies. The expression of HOXA11-AS is aberrantly altered in many cancers, either as a tumor suppressor or as a tumor accelerator. The different underlying mechanism of HOXA11-AS in different cancers (including, nonsmall cell lung cancers, osteosarcoma, uveal melanoma, glioma, hepatocellular carcinoma, gastric cancer, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, ovarian cancer, and glioblastoma) was also detailed. These findings lead us to conclude that HOXA11-AS participate in the complex network of cancers and plays an important role in the tumorigenesis and progression. Functional HOXA11-AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11-AS-targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers.

Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells.

BACKGROUND/AIMS: Diabetic cardiomyopathy is associated with increased apoptosis and suppressed autophagy in cardiac cells. The polyphenol resveratrol has shown beneficial effects in various cardiovascular diseases. This study investigated if resveratrol protected cardiac cells by modulating apoptosis and autophagy in the context of diabetes. METHODS: H9c2 cardiac myoblast cells were exposed to high glucose combined with palmitate. Autophagy was evaluated by estimating LC3-II/I ratio, P62 protein levels, and LC3 fluorescent puncta. Apoptosis was assessed by using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), flow cytometry, and analysis of the protein expression of apoptotic markers (cleavage of caspase-3 and PARP). RESULTS: High glucose and palmitate suppressed autophagic activity and exacerbated apoptotic cell death in cardiac myoblast cells. Resveratrol restored autophagy and attenuated apoptosis in cells upon diabetic stimuli. Moreover, resveratrol activated AMPK and JNK1, thereby suppressing mTOR and its downstream effectors p70S6K1 and 4EBP1, as well as disrupting the Beclin1-Bcl-2 complex. CONCLUSION: Resveratrol protects cardiac cells by regulating the switch between autophagy and apoptotic machinery under diabetic conditions, which is attributed by AMPK-mediated phosphorylation of mTORC1/p70S6K1/4EBP1 and JNK-mediated dissociation of Beclin1-Bcl-2. Our study suggests that autophagy may be an important target for resveratrol in the treatment of diabetic cardiomyopathy.

Recombinant immunotoxins with albumin-binding domains have long half-lives and high antitumor activity.

Recombinant immunotoxins (RITs) are chimeric proteins consisting of a Fv that binds to a cancer cell and a portion of a protein toxin. One of these, Moxetumomab pasudotox, was shown to be effective in treating patients with some leukemias, where the cells are readily accessible to the RIT. However, their short half-life limits their efficacy in solid tumors, because penetration into the tumors is slow. Albumin and agents bound to albumin have a long half-life in the circulation. To increase the time tumor cells are exposed to RITs, we have produced and evaluated variants that contain either an albumin-binding domain (ABD) from Streptococcus or single-domain antibodies from Llama. We have inserted these ABDs into RITs targeting mesothelin, between the Fv and the furin cleavage site. We find that these proteins can be produced in large amounts, are very cytotoxic to mesothelin-expressing cancer cell lines, and have a high affinity for human or mouse serum albumin. In mice, the RIT containing an ABD from Streptococcus has a longer half-life and higher antitumor activity than the other two. Its half-life in the circulation of mice ranges from 113 to 194 min compared with 13 min for an RIT with no ABD. Cell uptake studies show the RIT enters the target cell bound to serum albumin. We conclude that RITs with improved half-lives and antitumor activity should be evaluated for the treatment of cancer in humans.

The BRAF activated non-coding RNA: A pivotal long non-coding RNA in human malignancies.

Long non-coding RNAs (lncRNAs) participate in the complex network of cancer and play an important role in tumourigenesis and progression. BRAF activated non-coding RNA (BANCR), a 4-exon transcript of 693-bp, was first discovered as an oncogenic long non-coding RNA in BRAFV600E melanomas cells in 2012 and was related to melanoma cell migration. Besides melanoma, increasing evidence has explored the potential role of BANCR in the development and progression of multiple other human malignancies, such as retinoblastoma, lung cancer, gastric cancer etc. since its discovery. The expression pattern of BANCR varies in different types of cancers, either as a tumour suppressor or as an accelerator. Functional BANCR may serve as a promising biomarker for cancer diagnosis as well as prognosis evaluation. BANCR-targeted intervention may also become a valuable novel therapeutic tool against human malignancies. This review summarized the advanced research progresses concerning the expression and role of BANCR in different human malignancies.