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ABSTRACT Background Objective Methods Results Conclusion Aesthetic neuromodulator injections of the upper face are frequently performed to temporarily block muscular actions of the periorbital muscles to ultimately reduce skin rhytids. However, the adverse event rate in the literature for toxin‐induced blepharoptosis ranges from 0.51% to 5.4%.To identify access pathways by which injected neuromodulator product can travel from extra‐ to intra‐orbital and therefore affect the levator palpebrae superioris muscle.Nine non‐embalmed human body donors were investigated in this study with a mean age at death of 72.8 (16.1) years. The 18 supraorbital regions were injected in 28 times (14 for supratrochlear and 14 for supraorbital) with 0.5 cc, whereas eight cases (four for supratrochlear and four supraorbital) were injected with 0.1 cc of colored product. Anatomic dissections were conducted to identify structures stained by the injected color.The results of this injection‐ and dissection‐based study revealed that both the supratrochlear and the supraorbital neurovascular bundles are access pathways for injected neuromodulator products to reach the intra‐orbital space and affect the levator palpebrea superioris muscle. Out of 36 conducted injection passes, seven (19.44%) resulted in affection of the sole elevator of the eyelid of which 100% occurred only at an injection volume of 0.5 cc and not at 0.1 cc.Clinically, the results indicate that a low injection volume, a superficial injection for the supraorbital location, and angling the needle tip away from the supratrochlear foramen (toward the contralateral temple) when targeting the corrugator supercilii muscles, can increase the safety profile of an aesthetic toxin glabellar treatment. [ABSTRACT FROM AUTHOR]

John Lennon has an enduring, instantly recognisable, iconic, spectacle look. However, prior to 1966, he was rarely seen wearing glasses in public. From ages 7 to 26, he effectively hid his myopia away, including a period of unsuccessful contact lens wear during Beatlemania. This narrative review examines John's experience with contact lenses from 1963 to 1966 when he wore corneal rigid lenses made from polymethylmethacrylate, which regularly fell out. This frequent lens ejection was most likely due to the interaction between his upper eyelid and a spherical back surface rigid lens fitted to his right eye, which had a moderate degree of with‐the‐rule corneal astigmatism. John's recollection that his contact lenses stayed in place while 'stoned' supports this hypothesis, as a cannabis‐induced upper eyelid ptosis would reduce the likelihood of lens ejection. [ABSTRACT FROM AUTHOR]

Background: Double‐eyelid blepharoplasty is a popular cosmetic procedure in Asia; however, there are some drawbacks to this procedure for mild blepharoptosis. Enhancing movement of the levator aponeurosis can correct blepharoptosis through the release of fibrous web bands present between the preaponeurotic fat pad and levator aponeurosis. Aim: To improve our understanding of the anatomical link between the levator aponeurosis and orbital septum fat and to introduce that the release of the link can provide favorable results in double‐eyelid blepharoplasty. Patients/Methods: We included patients with latent ptosis or subclinical blepharoptosis who underwent double‐eyelid blepharoplasty with the release of fibrous web bands between June 2021 and March 2023. Mild ptosis was corrected following complete release of the fibrous bands beneath the preaponeurotic fat pad. Patients were followed up for 4–12 months postoperatively, and surgical outcomes were evaluated. Patient demographic variables and photographs were collected pre‐ and postoperatively. Patients, surgeons, and laypersons were asked to evaluate the outcomes postoperatively. The Friedman's nonparametric (for repeated measures) two‐way analysis of variance was used for statistical analyses. Results: Outcomes were assessed in 45 individuals with an average monitoring period of 6.9 months. There were no cases of incomplete eyelid closure or upper eyelid ectropion. Over 50% of the surgical outcomes were deemed "satisfactory" by each of the three groups in relation to the widening of the eyelid fissure. Most of the examined patients demonstrated favorable long‐term results. Conclusions: Fibrous web bands are implicated in subclinical or mild blepharoptosis. The release of fibrous web bands between the preaponeurotic fat pad and levator aponeurosis can provide favorable results in double‐eyelid blepharoplasty. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Filler injections into the upper eyelid may cause levator aponeurosis fibrosis and ptosis. This risk must be considered. When ptosis appears, treatment might be difficult. Understanding the upper eyelid anatomy and procedures is essential to prevent eyelid damage. Ptosis is a prevalent condition in cosmetic surgery that occurs due to malfunction of the levator palpebrae superioris or insufficient Müller muscle action. It is characterized by the upper eyelid edge appearing lower than usual when seen at eye level. Ptosis may be categorized into congenital and acquired forms. The primary cause of congenital ptosis is attributed to abnormalities of the levator palpebrae superioris muscle or the motor nerve innervation that controls it. The condition arises from atypical development and malfunction of the oculomotor system. Acquired ptosis may be classified into many categories including traumatic, neurogenic, myogenic, senile, mechanical, and fake ptosis. Currently, there is little documentation of ptosis resulting from the degeneration of the aponeurosis of the muscle in the upper eyelid. We received a case of ptosis caused by fibrosis of the levator palpebrae superioris aponeurotic membrane. We used the technique of levator palpebrae superioris great advancement. The levator palpebrae superioris—Müller muscle was folded to create a stable composite construction via the levator palpebrae superioris high progress. [ABSTRACT FROM AUTHOR]

Background: Eyelid ptosis is characterized by an inferior displacement of the upper eyelid when the eye assumes its primary position. Besides its aesthetic implications, ptosis can also adversely affect visual acuity. Objective: This study aimed to evaluate the simultaneous administration of IncobotulinumtoxinA (IncoBonTA) and hyaluronic acid effect in eyelid ptosis and ocular rejuvenation. Methods: A novel, non‐surgical technique for eyelid ptosis management involving IncoBonTA and hyaluronic acid the co‐administration within a single syringe, and applied using a cannula. Results: The dual action of IncoBonTA and hyaluronic acid in conjunction with the exact injection sites approaches improves overall aesthetic outcomes but also optimizes the restoration of eyelid functionality in palpebral ptosis. Conclusions: The functional balance achieved among the contributory muscles—primarily the orbicularis oculi (OO) and its antagonists, the frontal muscle and levator palpebrae superioris (LPS), yields to both, cosmetic and functional. [ABSTRACT FROM AUTHOR]

Background: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by morphological abnormalities and peripheral blood cytopenias, carrying a risk of progression to acute myeloid leukemia. Although ferroptosis is a promising target for MDS treatment, the specific roles of ferroptosis‐related genes (FRGs) in MDS diagnosis have not been elucidated. Methods: MDS‐related microarray data were obtained from the Gene Expression Omnibus database. A comprehensive analysis of FRG expression levels in patients with MDS and controls was conducted, followed by the use of multiple machine learning methods to establish prediction models. The predictive ability of the optimal model was evaluated using nomogram analysis and an external data set. Functional analysis was applied to explore the underlying mechanisms. The mRNA levels of the model genes were verified in MDS clinical samples by quantitative real‐time polymerase chain reaction (qRT‐PCR). Results: The extreme gradient boosting model demonstrated the best performance, leading to the identification of a panel of six signature genes: SREBF1, PTPN6, PARP9, MAP3K11, MDM4, and EZH2. Receiver operating characteristic curves indicated that the model exhibited high accuracy in predicting MDS diagnosis, with area under the curve values of 0.989 and 0.962 for the training and validation cohorts, respectively. Functional analysis revealed significant associations between these genes and the infiltrating immune cells. The expression levels of these genes were successfully verified in MDS clinical samples. Conclusion: Our study is the first to identify a novel model using FRGs to predict the risk of developing MDS. FRGs may be implicated in MDS pathogenesis through immune‐related pathways. These findings highlight the intricate correlation between ferroptosis and MDS, offering insights that may aid in identifying potential therapeutic targets for this debilitating disorder. [ABSTRACT FROM AUTHOR]

Purpose: To determine the changes in the lower eyelid position, following ptosis surgery of the upper eyelid of the same eye in blepharoptosis patients. Methods: This prospective interventional before and after study included patients aged more than 5 years with blepharoptosis. Margin reflex distance one (MRD‐1), MRD two (MRD‐2), and levator function were measured before and the 6 months after the surgery. Results: Sixty patients with blepharoptosis (33 congenital and 27 acquired) were recruited. The mean age was 21.61 ± 10.82 and 59.8 ± 13.73 years in congenital and acquired groups, respectively. The mean MRD‐1 improved from 1.95 ± 0.99 before treatment to 4.47 ± 0.47 after treatment (p < 0.001). The mean MRD‐2 improved from 5.57 ± 0.63 before treatment to 4.95 ± 0.51 after treatment (p < 0.001). There was no statistically significant difference in MRD‐1 and MRD‐2 changes between the two groups (p > 0.05) There was no statistically significant correlation between MRD‐2 changes and LF (r = −0.03. p = 0.83). Conclusion: Present study showed a significant improvement in the condition of the lower eyelid improved after upper eyelid ptosis surgery. [ABSTRACT FROM AUTHOR]

Background: The demand for nonsurgical facial rejuvenation options is growing, yet the periorbital region remains an area of relative unmet need. This review explores nonsurgical options for facial rejuvenation and the role of oxymetazoline hydrochloride ophthalmic solution, 0.1%, in treating age‐related blepharoptosis as part of periorbital rejuvenation. Methods: Advisors experienced in facial rejuvenation met to discuss existing literature on the upper face and periorbital rejuvenation and the role of oxymetazoline hydrochloride ophthalmic solution, 0.1%, in treating facial aging. Results: An array of nonsurgical options exist to address the signs of aging, including minimally invasive treatments, such as botulinum toxin injections and dermal fillers, and noninvasive therapy, such as lasers, chemical peels, and microdermabrasion. However, treating age‐related ptosis in periorbital rejuvenation is mainly addressed surgically. The newly approved α‐adrenergic receptor agonist oxymetazoline hydrochloride ophthalmic solution, 0.1%, provides a novel non‐interventional approach to blepharoptosis. Conclusions: Facial rejuvenation is highly sought‐after in this post‐pandemic era. Each nonsurgical treatment option has its advantages and drawbacks. A patient‐centered approach is necessary to select the appropriate procedure considering the patient's concerns and aesthetic sensibilities. The eyes are an area of primary concern for patients, yet surgery is the gold standard for treating ptosis. Oxymetazoline hydrochloride ophthalmic solution, 0.1%, is a safe and effective nonsurgical treatment for blepharoptosis. [ABSTRACT FROM AUTHOR]

Iron has been found to be involved in the tumor cell proliferation process, which can lead to the increased sensitivity of cancer cells to ferroptosis. Since erianin is associated with oxidative stress in hepatocellular carcinoma (HCC), we hypothesized that the therapeutic effect and mechanism of erianin on HCC is related to ferroptosis. HCC cells were stimulated with increase of erianin concentrations for 24 h, and the survival rates of Huh‐7 and HepG2 cells gradually decreased. After intervention with different doses of erianin, cell proliferation, clone number, and invasion were prominently decreased, apoptosis ratio was increased. Moreover, Nec‐1, CQ, and Z‐VAD had no effect on the cell viability induced by erianin, while the combination of ferroptosis inhibitors (deferoxamine mesylate, ferrostatin‐1, and liproxstatin‐1) and erianin prominently increased cell survival rate. Erianin pretreatment induced ferroptosis by enhancing reactive oxygen species, MDA, and Fe2+ levels, and reducing GSH levels. Erianin activated JAK2/STAT3 pathway and inhibited SLC7A11 and GPX4 expression, thereby inducing ferroptosis. Besides, tumor growth was significantly inhibited in the erianin‐treated mice, and there was no obvious toxicity in the mice. Erianin reduced proliferation and invasion of HCC cells by inducing ferroptosis by blocking the JAK2/STAT3/SLC7A11 pathway, thereby impeding tumor growth. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This unique case report of primary Sjogren's syndrome (pSS) shows bilateral ptosis and significant periorbital edema, compromising vision. To avoid misleading diagnosis, antibody tests must be evaluated and interpreted in the context of clinical findings. Primary Sjögren's syndrome is an idiopathic, autoimmune disorder involving the lacrimal and salivary glands characterized by both localized and systemic manifestations including xerostomia and keratoconjunctivitis sicca. Myasthenia Gravis (MG) is also an autoimmune disorder characterized by the development of auto‐antibodies against nicotinic acetylcholine receptors that causes decreased muscle response to stimulation. It usually presents with ptosis and generalized body weakness. Ophthalmological involvement is common in both disorders but ptosis is very rarely seen in pSS. We report the case of a 27‐year‐old woman presenting to our clinic with the complaint of ptosis and eyelid swelling. She also had a positive anti‐acetylcholine receptor antibody test and her initial presentation mimicked Myasthenia Gravis. Her autoimmune workup revealed a positive titer of Anti Ro SSA antibodies. Myasthenia Gravis was ruled out on electrodiagnostic studies which showed no decremental response, and pSS was confirmed on lip biopsy. Our case highlights that it is important to interpret the antibody test results in the context of clinical findings as we can have spurious results in autoimmune diseases. Autoimmune conditions can have varying presenting complaints hence, clinical judgment should always overrule diagnostic investigations and should thus guide patient management. [ABSTRACT FROM AUTHOR]

Summary: Glioma, the predominant form of central nervous system (CNS) malignancies, presents a significant challenge due to its high prevalence and low 5‐year survival rate. The efficacy of current treatment methods is limited by the presence of the blood–brain barrier, the immunosuppressive microenvironment, and other factors. Immunotherapy has emerged as a promising approach, as it can overcome the blood–brain barrier. A tumor's immune privilege, which is induced by an immunosuppressive environment, constricts immunotherapy's clinical impact in glioma. Pyroptosis, a programmed cell death mechanism facilitated by gasdermins, plays a significant role in the management of glioma. Its ability to initiate and regulate tumor occurrence, progression, and metastasis is well‐established. However, it is crucial to note that uncontrolled or excessive cell death can result in tissue damage, acute inflammation, and cytokine release syndrome, thereby potentially promoting tumor advancement or recurrence. This paper aims to elucidate the molecular pathways involved in pyroptosis and subsequently discuss its induction in cancer therapy. In addition, the current treatment methods of glioma and the use of pyroptosis in these treatments are introduced. It is hoped to provide more ideas for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Summary: Necroptosis is generally considered as an inflammatory cell death form. The core regulators of necroptotic signaling are receptor‐interacting serine–threonine protein kinases 1 (RIPK1) and RIPK3, and the executioner, mixed lineage kinase domain‐like pseudokinase (MLKL). Evidence demonstrates that necroptosis contributes profoundly to inflammatory respiratory diseases that are common public health problem. Necroptosis occurs in nearly all pulmonary cell types in the settings of inflammatory respiratory diseases. The influence of necroptosis on cells varies depending upon the type of cells, tissues, organs, etc., which is an important factor to consider. Thus, in this review, we briefly summarize the current state of knowledge regarding the biology of necroptosis, and focus on the key molecular mechanisms that define the necroptosis status of specific cell types in inflammatory respiratory diseases. We also discuss the clinical potential of small molecular inhibitors of necroptosis in treating inflammatory respiratory diseases, and describe the pathological processes that engage cross talk between necroptosis and other cell death pathways in the context of respiratory inflammation. The rapid advancement of single‐cell technologies will help understand the key mechanisms underlying cell type‐specific necroptosis that are critical to effectively treat pathogenic lung infections and inflammatory respiratory diseases. [ABSTRACT FROM AUTHOR]

Summary: Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies. [ABSTRACT FROM AUTHOR]

Summary: Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), which correlates to the mitochondrial tricarboxylic acid (TCA) cycle, resulting in proteotoxic stress and eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts an indispensable role in cancer progression, which is considered a promising strategy for cancer therapy. Cancer immunotherapy has gained extensive attention owing to breakthroughs in immune checkpoint blockade; furthermore, cuproptosis is strongly connected to the modulation of antitumor immunity. Thus, a thorough recognition concerning the mechanisms involved in the modulation of copper metabolism and cuproptosis may facilitate improvement in cancer management. This review outlines the cellular and molecular mechanisms and characteristics of cuproptosis and the links of the novel regulated cell death modality with human cancers. We also review the current knowledge on the complex effects of cuproptosis on antitumor immunity and immune response. Furthermore, potential agents that elicit cuproptosis pathways are summarized. Lastly, we discuss the influence of cuproptosis induction on the tumor microenvironment as well as the challenges of adding cuproptosis regulators to therapeutic strategies beyond traditional therapy. [ABSTRACT FROM AUTHOR]

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM. [ABSTRACT FROM AUTHOR]

This review article explores the relationship between the NOD‐like receptor protein 3 (NLRP3) inflammasome and the risk of developing polycystic ovary syndrome (PCOS). The NLRP3 inflammasome, a fundamental element of the innate immune system, plays a crucial role in the production of proinflammatory mediators and pyroptosis, a type inflammatory cell death. We conducted a thorough search on scientific databases to gather relevant information on this topic, utilizing relevant keywords. The reviewed studies indicated a correlation between PCOS and a higher incidence of granulosa cell (GC) death and the presence of ovarian tissue fibrosis. NLRP3 inflammasome stimulation and subsequent pyroptosis in GCs play a significant role in the pathophysiology of PCOS. Active NLRP3 inflammasome is involved in the production of inflammatory mediators like interleukin‐1β (IL‐1β) and IL‐18, contributing to the development of PCOS, particularly in overweight patients. Therefore, inhibiting NLRP3 activation and pyroptosis could potentially offer novel therapeutic strategies for PCOS. Some limited studies have explored the use of agents with antioxidant and anti‐inflammatory properties, as well as gene therapy approaches, to target the NLRP3 and pyroptosis signaling pathways. This study overview the understanding of the relationship between NLRP3 inflammasome activation, pyroptosis, and PCOS. It highlights the potential of targeting the NLRP3 inflammasome as an approach for treating PCOS. Nonetheless, further research and clinical trials are imperative to validate these results and explore the effectiveness of NLRP3 inflammasome inhibition in the management of PCOS. [ABSTRACT FROM AUTHOR]

Background: PANoptosis is a novel form of programmed cell death (PCD) found in 2019 that is regulated by the PANoptosome. PANoptosis combines essential features of pyroptosis, apoptosis, and necroptosis, forming a "death triangle" of cells. While apoptosis, pyroptosis, and necroptosis have been extensively studied for their roles in human inflammatory diseases and many other clinical conditions, historically they were considered as independent processes. However, emerging evidence indicates that these PCDs exhibit cross talk and interactions, resulting in the development of the concept of PANoptosis. Methods: In this review, we offer a concise summary of the fundamental mechanisms of apoptosis, pyroptosis, and necroptosis. We subsequently introduce the notion of PANoptosis and detail the assembly mechanism of the PANoptosome complex which is responsible for inducing cell death. We also describe some regulatory networks of PANoptosis. Results: PANoptosis now has been associated with various human diseases including cancer. Although the exact function of PANoptosis in each tumor is not fully understood, it represents a prospective avenue for cancer therapy, offering promise for advancements in cancer therapy. Conclusions: In the future, in‐depth study of PANoptosis will continue to help us in understanding the fundamental processes underlying cell death and provide scientific support for cancer research. [ABSTRACT FROM AUTHOR]

Pyroptosis is an inflammasome‐dependent form of programmed cell death that is mediated by caspases‐1, ‐4, ‐5, and ‐11, and the gasdermin protein family. It is characterized by the rupture of cell membrane and the subsequent release of cell contents and interleukins, leading to inflammatory reaction and activation of the immune system. Recent studies have suggested that pyroptosis plays a role in the development of gastrointestinal tumors, impeding tumor generation and progression as well as providing a favorable microenvironment for tumor growth. In this review we outlined the current knowledge regarding the implications of pyroptosis in gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Summary: A 9‐month‐old Thoroughbred colt was presented to the University College Dublin Veterinary Hospital for investigation of suspected neck pain. Clinical signs included severe dullness, bilateral mucopurulent nasal discharge, ptosis of the right eyelid, reduced range of motion of the neck and ataxia. Endoscopy of the medial compartment of both guttural pouches showed fungal‐like plaques, from which Aspergillus was cultured. Laser salpingopharyngeal fistulation was performed under standing sedation and the colt received treatment with oral potassium iodide. The colt developed bacteraemia post‐operatively which resolved after antimicrobial treatment. Serial endoscopic evaluation of the guttural pouches showed complete resolution of fungal plaques 4 months post‐operatively. Minimal neurologic deficits remained 6 months post‐operatively. This report highlights the importance of considering guttural pouch mycosis in young horses and those presenting with reduced range of neck motion and neck pain. It offers support for the use of salpingopharyngostomy as an effective treatment method for guttural pouch mycosis and documents its use in the case of bilateral disease confirmed by fungal culture. It also documents the recovery of a horse from GPM with associated severe neurological signs. [ABSTRACT FROM AUTHOR]

Aim: Congenital myasthenic syndromes (CMS) are a rare and diverse group of treatable neuromuscular transmission disorders. Diagnosis is often substantially delayed. This study aimed to identify common symptoms of CMS in children and their manifestation to aid diagnosis and early intervention. Methods: We performed a retrospective cohort study, including 18 children (median age 13 years, range 9 years 5 months–18 years 0 month) with CMS. Data on CMS symptoms and their manifestation were extracted from patients' charts and supplemented with parental telephone interviews. Descriptive analyses were used to identify common symptoms. Results: A median diagnostic delay of 4 years and 7 months (interquartile range: 51 months) was observed. Proximal muscle weakness (100%), ptosis (89%), clumsy gait (82%), difficulty eating solid foods (78%) and recurrent respiratory tract infections (72%) were most common in these patients. Symptoms mostly co‐occurred and frequently had a fluctuating character, aggravated by infections or fatigue. Conclusion: Early referral to diagnose CMS is crucial to enable timely initiation of treatment. Heightened attention to a combination of symptoms related to muscle weakness, rather than individual symptoms, should support paediatricians in flagging these neuromuscular disorders. Medical history taking should be tailored to parents' perceptions, asking questions about recognisable symptoms of muscle weakness. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal cancer poses a serious health threat owing to its high morbidity and mortality. Although immune checkpoint blockade (ICB) therapies have achieved meaningful success in most solid tumors, the improvement in survival in gastrointestinal cancers is modest, owing to sparse immune response and widespread resistance. Metabolic reprogramming, autophagy, and ferroptosis are key regulators of tumor progression. Methods: A literature review was conducted to investigate the role of the metabolic reprogramming, autophagy, and ferroptosis in immunotherapy resistance of gastrointestinal cancer. Results: Metabolic reprogramming, autophagy, and ferroptosis play pivotal roles in regulating the survival, differentiation, and function of immune cells within the tumor microenvironment. These processes redefine the nutrient allocation blueprint between cancer cells and immune cells, facilitating tumor immune evasion, which critically impacts the therapeutic efficacy of immunotherapy for gastrointestinal cancers. Additionally, there exists profound crosstalk among metabolic reprogramming, autophagy, and ferroptosis. These interactions are paramount in anti‐tumor immunity, further promoting the formation of an immunosuppressive microenvironment and resistance to immunotherapy. Conclusions: Consequently, it is imperative to conduct comprehensive research on the roles of metabolic reprogramming, autophagy, and ferroptosis in the resistance of gastrointestinal tumor immunotherapy. This understanding will illuminate the clinical potential of targeting these pathways and their regulatory mechanisms to overcome immunotherapy resistance in gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF‐β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus‐mediated gain‐of‐function studies of TGF‐β and MST1 were applied to validate the roles of TGF‐β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF‐β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF‐β in either in vitro or mouse‐transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF‐β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM), which has a high incidence and several harmful consequences, poses a severe danger to human health. Research on the function of ferroptosis in T2DM is increasing. This study uses bioinformatics techniques identify new diagnostic T2DM biomarkers associated with ferroptosis. Methods: To identify ferroptosis‐related genes (FRGs) that are differentially expressed between T2DM patients and healthy individuals, we first obtained T2DM sequencing data and FRGs from the Gene Expression Omnibus (GEO) database and FerrDb database. Then, drug‐gene interaction networks and competitive endogenous RNA (ceRNA) networks linked to the marker genes were built after marker genes were filtered by two machine learning algorithms (LASSO and SVM‐RFE algorithms). Finally, to confirm the expression of marker genes, the GSE76895 dataset was utilized. The protein and RNA expression of some marker genes in T2DM and nondiabetic tissues was also examined by Western blotting, immunohistochemistry (IHC), immunofluorescence (IF) and quantitative real‐time PCR (qRT‐PCR). Results: We obtained 58 differentially expressed genes (DEGs) associated with ferroptosis. GO and KEGG enrichment analyses showed that these DEGs were significantly enriched in hypoxia and ferroptosis. Subsequently, eight marker genes (SCD, CD44, HIF1A, BCAT2, MTF1, HILPDA, NR1D2, and MYCN) were screened by LASSO and SVM‐RFE machine learning algorithms, and a model was constructed based on these eight genes. This model also has high diagnostic power. In addition, based on these eight genes, we obtained 48 drugs and constructed a complex ceRNA network map. Finally, Western blotting, IHC, IF, and qRT‐PCR results of clinical samples further confirmed the results of public databases. Conclusions: The diagnosis and aetiology of T2DM can be greatly aided by eight FRGs, providing novel therapeutic avenues. [ABSTRACT FROM AUTHOR]

Metal‐based nanomaterials have attracted broad attention recently due to their unique biological physical and chemical properties after entering tumor cells, namely biological effects. In particular, the abilities of Ca2+ to modulate T cell receptors activation, K+ to regulate stem cell differentiation, Mn2+ to activate the STING pathway, and Fe2+/3+ to induce tumor ferroptosis and enhance catalytic therapy, make the metal ions and metal‐based nanomaterials play crucial roles in the cancer treatments. Therefore, due to the superior advantages of metal‐based nanomaterials and the characteristics of the tumor microenvironment, we will summarize the recent progress of the anti‐tumor biological effects of metal‐based nanomaterials. Based on the different effects of metal‐based nanomaterials on tumor cells, this review mainly focuses on the following five aspects: (1) metal‐enhanced radiotherapy sensitization, (2) metal‐enhanced catalytic therapy, (3) metal‐enhanced ferroptosis, (4) metal‐enhanced pyroptosis, and (5) metal‐enhanced immunotherapy. At the same time, the shortcomings of the biological effects of metal‐based nanomaterials on tumor therapy are also discussed, and the future research directions have been prospected. The highlights of promising biosafety, potent efficacy on biological effects for tumor therapy, and the in‐depth various biological effects mechanism studies of metal‐based nanomaterials provide novel ideas for the future biological application of the nanomaterials. [ABSTRACT FROM AUTHOR]

Therefore, it would seem that the appropriate description of the upper lid movement in the patient reported by Ordás et al[1] is lid myorhythmia rather than lid nystagmus. Interestingly, this can be maximal with the lids lightly or incompletely closed.[6] In each of these three types of lid nystagmus there is a rapid upward movement of the lid followed by a slower downward restoration of the lid position. In this issue, Ordás and colleagues[1] report a case of "eyelid nystagmus" in a 75-year-old woman presenting with 5 years progressive gait disorder on a background of hypertension. [Extracted from the article]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the cause the ongoing pandemic of coronavirus disease 2019 (COVID19). One key feature associated with COVID‐19 is excessive pro‐inflammatory cytokine production that leads to severe acute respiratory distress syndrome. Although the cytokine storm induces inflammatory cell death in the host, which type of programmed cell death mechanism that occurs in various organs and cells remains elusive. Using an in vitro culture model of polarized human airway epithelium (HAE), we observed that necroptosis, but not apoptosis or pyroptosis, plays an essential role in the damage of the epithelial barrier of polarized HAE infected with SARS‐CoV‐2. Pharmacological inhibitors of necroptosis, necrostatin‐2 and necrosulfonamide, efficiently prevented cell death and epithelial barrier dysfunction caused by SARS‐CoV‐2 infection. Moreover, the silencing of genes that are involved in necroptosis, RIPK1, RIPK3, and MLKL, ameliorated airway epithelial damage of the polarized HAE infected with SARS‐CoV‐2. This study, for the first time, confirms that SARS‐CoV‐2 infection triggers necroptosis that disrupts the barrier function of human airway epithelia in vitro. [ABSTRACT FROM AUTHOR]

Oncogene‐induced hyper‐proliferation in cancer cells is accompanied by the onset of different stresses, including DNA‐replication stress, metabolic stress and oxidative stress. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal and contradictory role in tumor progression. ROS dictates a multitude of cell signaling pathways to facilitate the malignant transformation of tumor cells. In the meantime, oxidative burden in tumor cells mandates reinforcing antioxidant capacity to mitigate detrimental damages. The addiction to oxidative stress and increased iron demands in cancer cells also impinges on the sensitivity of ferroptosis. Targeting redox homeostasis and ferroptosis to overcome drug resistance in cancer treatment has become an attractive research topic. However, the roles of oncogenic signaling in redox regulation and ferroptosis have not been comprehensively discussed. In this review, we summarize current knowledge regarding the interplay between redox regulation and ferroptosis in the context of cancer biology. We emphasize the implication of oncogenic signaling in redox homeostasis and ferroptosis regulation. We also provide an overview of strategies targeting oxidative stress and ferroptosis in cancer treatment. [ABSTRACT FROM AUTHOR]

Cyclic GMP‐AMP synthase (cGAS) monitors dsDNA in the cytosol in response to pathogenic invasion or tissue injury, initiating cGAS‐STING signaling cascades that regulate various cellular physiologies, including IFN /cytokine production, autophagy, protein synthesis, metabolism, senescence, and distinct types of cell death. cGAS‐STING signaling is crucial for host defense and tissue homeostasis; however, its dysfunction frequently leads to infectious, autoimmune, inflammatory, degenerative, and cancerous diseases. Our knowledge regarding the relationships between cGAS‐STING signaling and cell death is rapidly evolving, highlighting their essential roles in pathogenesis and disease progression. Nevertheless, the direct control of cell death by cGAS‐STING signaling, rather than IFN/NF‐κB‐mediated transcriptional regulation, remains relatively unexplored. This review examines the mechanistic interplays between cGAS‐STING cascades and apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagic/lysosomal cell death. We will also discuss their pathological implications in human diseases, particularly in autoimmunity, cancer, and organ injury scenarios. We hope that this summary will stimulate discussion for further exploration of the complex life‐or‐death responses to cellular damage mediated by cGAS‐STING signaling. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 76-year-old woman experiencing sudden-onset, painless ptosis in the right eye as an early symptom of a thalamic stroke, with no other neurological deficits. Topics discussed include the vascular territories of the thalamus and how infarcts in these regions can lead to varied neuro-ophthalmological symptoms, diagnostic imaging approaches, and the patient's positive response to dual antiplatelet therapy.

Ferroptosis, a novel type of cell death mediated by the iron‐dependent lipid peroxidation, contributes to the pathogenesis of the intervertebral disc degeneration (IDD). Increasing evidence demonstrated that melatonin (MLT) displayed the therapeutic potential to prevent the development of IDD. Current mechanistic study aims to explore whether the downregulation of ferroptosis contributes to the therapeutic capability of MLT in IDD. Current studies demonstrated that conditioned medium (CM) from the lipopolysaccharide (LPS)‐stimulated macrophages caused a series of changes about IDD, including increased intracellular oxidative stress (increased reactive oxygen species and malondialdehyde levels, but decreased glutathione levels), upregulated expression of inflammation‐associated factors (IL‐1β, COX‐2 and iNOS), increased expression of key matrix catabolic molecules (MMP‐13, ADAMTS4 and ADAMTS5), reduced the expression of major matrix anabolic molecules (COL2A1 and ACAN), and increased ferroptosis (downregulated GPX4 and SLC7A11 levels, but upregulated ACSL4 and LPCAT3 levels) in nucleus pulposus (NP) cells. MLT could alleviate CM‐induced NP cell injury in a dose‐dependent manner. Moreover, the data substantiated that intercellular iron overload was involved in CM‐induced ferroptosis in NP cells, and MLT treatment alleviated intercellular iron overload and protected NP cells against ferroptosis, and those protective effects of MLT in NP cells further attenuated with erastin and enhanced with ferrostatin‐1(Fer‐1). This study demonstrated that CM from the LPS‐stimulated RAW264.7 macrophages promoted the NP cell injury. MLT alleviated the CM‐induced NP cell injury partly through inhibiting ferroptosis. The findings support the role of ferroptosis in the pathogenesis of IDD, and suggest that MLT may serve as a potential therapeutic approach for clinical treatment of IDD. [ABSTRACT FROM AUTHOR]

Objective: To determine the pathogenesis and molecular targets of anaphylaxis caused by hydatid cyst fluid leakage. Methods: First, Balb/c mice were infected with Echinococcus granulosus, and then the anaphylaxis model was developed. The mice were separated into: anaphylaxis caused by the cystic echinococcosis group (ANPC), the cystic echinococcosis without anaphylaxis group (CE group), and the normal control group (CTRL). Following this, the spleen tissue was collected for microRNA (miRNA) sequencing. Using bioinformatics analysis, differentially expressed miRNAs (DEMs) were identified. Then, through the use of protein–protein interaction (PPI) networks, the key target genes for miRNA regulation associated with echinococcosis‐induced anaphylaxis were identified. Results: ANPC and CE groups have 29 and 39 DEMs compared to the CTRL group, respectively. Based on these 25 DEMs, interactions between miRNA and mRNA were screened, and 174 potential target genes were identified. We performed gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on these 174 target genes, and the results revealed that the three pathways with the highest enrichment were the PI3K‐Akt signaling pathway, FoxO signaling pathway, and Focal adhesion. The interaction analysis of PPI and miRNA‐hub gene networks revealed that interleukin 6 (IL‐6) was regulated by miR‐146a‐5p and miR‐149‐5p, while IL‐10 was regulated by miR‐29b‐3p and miR‐29c‐3. Using reverse transcription polymerase chain reaction, we found that the miRNAs regulating IL‐6 and IL‐10 were significantly upregulated in the ANPC group, and there are three pathways involved in that process: Pathways of PI3K‐Akt signaling, FoxO signaling, and Focal adhesion. IL‐6 and IL‐10 play an important role in cellular pyroptosis and apoptosis. Therefore, the aforementioned results provide significant reference value for elucidating the mechanism of cellular pyroptosis and apoptosis in echinococcosis‐induced anaphylaxis, and for formulating tissue and organ protection strategies for patients with cystic echinococcosis when anaphylaxis is triggered by hydatid cyst rupture. [ABSTRACT FROM AUTHOR]

Background: A novel form of cell death termed cuproptosis was proposed recently. miRNAs play important roles in colorectal cancer (CRC). However, their relationships have not been reported. Methods: miRNAs that negatively regulate 16 cuproptosis regulators were predicted using Targetscan database. The univariate Cox, LASSO, and multivariate Cox regression analyses were performed to select cuproptosis‐related miRNAs. GSEA and ssGSEA analysis was carried out for functional enrichment analysis. The immune cell proportion score (IPS) and the efficiencies of multiple chemotherapy drugs were compared between different risk groups. The CCK8, cell colony, edu, and flow cytometry assays were performed to validate the roles of miRNA. Luciferase reporter assay confirmed the regulatory mechanism of miRNA on cuproptosis. Results: Six cuproptosis‐related miRNAs (hsa‐miR‐653, hsa‐miR‐216a, hsa‐miR‐3684, hsa‐miR‐4437, hsa‐miR‐641, and hsa‐miR‐552) were screened out for model construction. The risk score could act as an independent prognostic indicator in CRC (p < 0.001, 95% HR = 1.243 (1.129–1.369)). The nomogram could efficiently predict the overall survival rate (AUC = 0.836). Then, the level of immunosuppressive pathways, immunosuppressive cells, stromal‐activated genes, and stromal score was higher in the high‐risk group. The IPS analysis showed a better response to immunotherapy in the low‐risk group. Also, the risk score was closely correlated with efficiencies of multiple chemotherapy drugs. Furthermore, miR‐653 was highly expressed in CRC tissues (p < 0.001), closely correlated with T stage (p < 0.001), metastasis (p < 0.001), and tumor stage (p < 0.001). High expression of miR‐653 predicted a shorter overall survival (p = 0.0282) and disease‐free survival (p = 0.0056). In addition, miR‐653 promoted cell proliferation, inhibited apoptosis, and negatively regulated the expression of DLD through directly binding to the 3'‐UTR of DLD mRNA. Conclusion: We constructed a cuproptosis‐related miRNA signature for the prediction of CRC patient survival and immunotherapy sensitivity. miR‐653 was highly expressed in CRC tissues, promoted cell proliferation, and inhibited apoptosis by negatively regulating the expression of DLD. [ABSTRACT FROM AUTHOR]

Background: Severe community‐acquired pneumonia (SCAP) is one of the world's most common diseases and a major etiology of acute respiratory distress syndrome (ARDS). Cuproptosis is a novel form of regulated cell death that can occur in various diseases. Methods: Our study explored the degree of immune cell infiltration during the onset of severe CAP and identified potential biomarkers related to cuproptosis. Gene expression matrix was obtained from GEO database indexed GSE196399. Three machine learning algorithms were applied: The least absolute shrinkage and selection operator (LASSO), the random forest, and the support vector machine‐recursive feature elimination (SVM‐RFE). Immune cell infiltration was quantified by single‐sample gene set enrichment analysis (ssGSEA) scoring. Nomogram was constructed to verify the applicability of using cuproptosis‐related genes to predict the onset of severe CAP and its deterioration toward ARDS. Results: Nine cuproptosis‐related genes were differentially expressed between the severe CAP group and the control group: ATP7B, DBT, DLAT, DLD, FDX1, GCSH, LIAS, LIPT1, and SLC31A1. All 13 cuproptosis‐related genes were involved in immune cell infiltration. A three‐gene diagnostic model was constructed to predict the onset of severe CAP: GCSH, DLD, and LIPT1. Conclusion: Our study confirmed the involvement of the newly discovered cuproptosis‐related genes in the progression of SCAP. [ABSTRACT FROM AUTHOR]

Aim: Pyroptosis is a type of inflammatory cell death and is related to pulpitis and apical periodontitis. In this study, the aim was to investigate how periodontal ligament fibroblasts (PDLFs) and dental pulp cells (DPCs) respond to pyroptotic stimuli and explore whether dimethyl fumarate (DMF) could block pyroptosis in PDLFs and DPCs. Methodology: Three methods (stimulation with lipopolysaccharide [LPS] plus nigericin, poly(dA:dT) transfection and LPS transfection) were used to induce pyroptosis in PDLFs and DPCs, two types of fibroblasts related to pulpitis and apical periodontitis. THP‐1 cell was used as a positive control. Afterwards, PDLFs and DPCs were treated with or without DMF before inducing pyroptosis to examine the inhibitory effect of DMF. Pyroptotic cell death was measured by lactic dehydrogenase (LDH) release assays, cell viability assays, propidium iodide (PI) staining and flow cytometry. The expression levels of cleaved gasdermin D N‐terminal (GSDMD NT), caspase‐1 p20, caspase‐4 p31 and cleaved PARP were examined by immunoblotting. Immunofluorescence analysis was used to detect the cellular distribution of GSDMD NT. Results: Periodontal ligament fibroblasts and DPCs were more sensitive to cytoplasmic LPS‐induced noncanonical pyroptosis than to canonical pyroptosis induced by stimulation with LPS priming plus nigericin or by poly(dA:dT) transfection. In addition, treatment with DMF attenuated cytoplasmic LPS‐induced pyroptotic cell death in PDLFs and DPCs. Mechanistically, it was shown that the expression and plasma membrane translocation of GSDMD NT were inhibited in DMF‐treated PDLFs and DPCs. Conclusions: This study indicates that PDLFs and DPCs are more sensitive to cytoplasmic LPS‐induced noncanonical pyroptosis and that DMF treatment blocks pyroptosis in LPS‐transfected PDLFs and DPCs by targeting GSDMD, suggesting DMF might be a promising drug for the management of pulpitis and apical periodontitis. [ABSTRACT FROM AUTHOR]

Genetics, age, environmental factors, and oxidative stress have all been implicated in the development of Parkinson's disease (PD); however, a complete understanding of its pathology remains elusive. At present, there is no cure for PD, and currently available therapeutics are insufficient to meet patient needs. Ferroptosis, a distinctive iron‐dependent cell death mode characterized by lipid peroxidation and oxidative stress, has pathophysiological features similar to those of PD, including iron accumulation, reactive oxygen species‐induced oxidative damage, and mitochondrial dysfunction. Ferroptosis has been identified as a specific pathway of neuronal death and is closely related to the pathogenesis of PD. Despite the similarities in the biological targets involved in PD pathogenesis and ferroptosis, the relationship between novel targets in PD and ferroptosis has been neglected in the literature. In this review, the mechanism of ferroptosis is discussed, and the potential therapeutic targets implicated in both PD and ferroptosis are compared. Furthermore, the anti‐PD effects of several ferroptosis inhibitors, as well as clinical studies thereof, and the identification of novel lead compounds for the treatment of PD and the inhibition of ferroptosis are reviewed. It is hoped that this review can promote research to further elucidate the relationship between ferroptosis and PD and provide new strategies for the development of novel ferroptosis‐targeting PD therapy. [ABSTRACT FROM AUTHOR]

Background: Congenital myasthenic syndromes (CMS) are rare inherited heterogeneous disorders of neuromuscular transmission. Aims and methodology: This study aims to describe clinical and investigative characteristics including genetic aspects of patients with congenital myasthenic syndrome (CMS), in a cohort from western India. Retrospective analysis for the study period of 9 years (−January 2013 to December 2021) was performed. Patients were identified by predefined selection criteria using a combination of clinical, electrophysiological, and genetic studies. Results: Fifteen genetically evaluated CMS patients, 11 females, and 4 males were identified. Ten patients had a history of fatigable ptosis at an early age, whereas all patients had varying degrees of proximal weakness at the time of presentation. The mean age at onset was 16 years and the mean age at final diagnosis was 22 years, thereby representing a mean delay in diagnosis of 6 years. Among the total 13 different genetic mutations identified, 4 are not previously reported. The most common genetic mutations identified were CHRNE gene (in 7 patients) followed by DOK7 gene (in 6 patients), and the remaining 2 patients had mutation in MUSK gene. Roma founder mutation (c.1327delG, p.E443ter) was seen in 5 patients with CHRNE gene. Four patients responded to pyridostigmine alone, 7 patients to salbutamol, whereas 4 patients required a combination of pyridostigmine and salbutamol. Conclusion: This study, carried out in a small cohort of patients, highlights the frequent occurrence of Roma founder mutation in our population, and the predominance of CHRNE and DOK7 gene mutations, points of regional importance. Four novel variants were also identified in the genetic studies carried out. [ABSTRACT FROM AUTHOR]

Cardio‐metabolic‐diseases (cardio‐metabolic‐diseases) are leading causes of death and disability worldwide and impose a tremendous burden on whole society as well as individuals. As a new type of regulated cell death (RCD), ferroptosis is distinct from several classical types of RCDs such as apoptosis and necroptosis in cell morphology, biochemistry, and genetics. The main molecular mechanisms of ferroptosis involve iron metabolism dysregulation, mitochondrial malfunction, impaired antioxidant capacity, accumulation of lipid‐related peroxides and membrane disruption. Within the past few years, mounting evidence has shown that ferroptosis contributes to the pathophysiological process in cardio‐metabolic‐diseases. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This review comprehensively summarizes the mechanism of ferroptosis in the development and progression of cardio‐metabolic‐diseases, so as to provide new insights for cardio‐metabolic‐diseases pathophysiology. Moreover, we highlight potential druggable molecules in ferroptosis signaling pathway, and discuss recent advances in management strategies by targeting ferroptosis for prevention and treatment of cardio‐metabolic‐diseases. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication of diabetes that severely affects the quality of life of diabetic patients. Long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of DCM. However, the role of the lncRNA homeobox transcript antisense RNA (HOTAIR) in the progression of DCM remains unclear. The present study aimed to investigate the role of HOTAIR in high glucose (HG)‐induced pyroptosis in cardiomyocytes. The expression of the lncRNA HOTAIR, FUS, and SIRT3 in H9C2 cardiomyocytes was detected by RT–qPCR. Western blotting was used to evaluate the expression of FUS and SIRT3 as well as that of pyroptosis‐ and inflammation‐related proteins. RT–qPCR and ELISA were used to determine the expression and secretion of IL‐1β and IL‐18. RNA pulldown and RIP experiments were used to validate the binding relationship among HOTAIR, FUS, and SIRT3. Flow cytometry was performed to detect pyroptosis. HG induced pyroptosis and elevated the expression of proteins associated with pyroptosis and inflammation (NLRP3, GSDMD‐N, cleaved caspase‐1, IL‐1β, and IL‐18) in cardiomyocytes. HOTAIR and SIRT3 levels were decreased in HG‐exposed H9C2 cells. Additionally, overexpression of HOTAIR inhibited the HG‐induced pyroptosis and inflammatory response in cardiomyocytes. HOTAIR upregulated SIRT3 expression in H9C2 cells by targeting FUS. Moreover, SIRT3 upregulation suppressed HG‐mediated pyroptosis of cardiomyocytes. Notably, SIRT3 depletion reversed the inhibitory effect of HOTAIR on HG‐triggered pyroptosis in cardiomyocytes. Our research indicates that HOTAIR alleviates pyroptosis in diabetic cardiomyocytes through the FUS/SIRT3 axis, providing a potential marker for the diagnosis and treatment of DCM. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by dystrophin mutations, leading to the loss of sarcolemmal integrity, and resulting in progressive myofibre necrosis and impaired muscle function. Our previous studies suggest that lipin1 is important for skeletal muscle regeneration and myofibre integrity. Additionally, we discovered that mRNA expression levels of lipin1 were significantly reduced in skeletal muscle of DMD patients and the mdx mouse model. To understand the role of lipin1 in dystrophic muscle, we generated dystrophin/lipin1 double knockout (DKO) mice, and compared the limb muscle pathology and function of wild‐type B10, muscle‐specific lipin1 deficient (lipin1Myf5cKO), mdx and DKO mice. We found that further knockout of lipin1 in dystrophic muscle exhibited a more severe phenotype characterized by increased necroptosis, fibrosis and exacerbated membrane damage in DKO compared to mdx mice. In barium chloride‐induced muscle injury, both lipin1Myf5cKO and DKO showed prolonged regeneration at day 14 post‐injection, suggesting that lipin1 is critical for muscle regeneration. In situ contractile function assays showed that lipin1 deficiency in dystrophic muscle led to reduced specific force production. Using a cell culture system, we found that lipin1 deficiency led to elevated expression levels of necroptotic markers and medium creatine kinase, which could be a result of sarcolemmal damage. Most importantly, restoration of lipin1 inhibited the elevation of necroptotic markers in differentiated primary lipin1‐deficient myoblasts. Overall, our data suggests that lipin1 plays complementary roles in myofibre stability and muscle function in dystrophic muscles, and overexpression of lipin1 may serve as a potential therapeutic strategy for dystrophic muscles. Key points: We identified that lipin1 mRNA expression levels are significantly reduced in skeletal muscles of Duchenne muscular dystrophy patients and mdx mice.We found that further depletion of lipin1 in skeletal muscles of mdx mice induces more severe dystrophic phenotypes, including enhanced myofibre sarcolemma damage, muscle necroptosis, inflammation, fibrosis and reduced specific force production.Lipin1 deficiency leads to elevated expression levels of necroptotic markers, whereas restoration of lipin1 inhibits their expression.Our results suggest that lipin1 is functionally complementary to dystrophin in muscle membrane integrity and muscle regeneration. [ABSTRACT FROM AUTHOR]

SARS‐CoV‐2 triggers inflammasome‐dependent release of pro‐inflammatory cytokine IL‐1β and pyroptosis, therefore, contributes to the huge inflammatory response observed in severe COVID‐19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID‐19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID‐19 patients and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID‐19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID‐19 pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. Methods: A retrospective study was undertaken over a period of 100 months. Ninety‐nine histopathologically proven cases of eyelid SGC available for follow‐up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. Results: Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High‐risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI‐1.65–5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96–17.19%, p < 0.01) and disease‐free survival (HR 4.61, 95% CI 2.81–7.54). The Kaplan–Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour‐related deaths (p < 0.01) and reduced disease‐free survival (p = 0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease‐free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. Conclusion: Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death. [ABSTRACT FROM AUTHOR]

Introduction: Facial aging is a multifactorial process in which considerable changes occur in different face structures. Thread lifting is one of the most common minimally invasive treatments related to facial rejuvenation. This study aimed to evaluate the efficacy and safety of jawline, jaw angle, and marionette lines correction in combination with APTOS threads and ELLANSE M types through an innovative technique. Materials and Methods: In this prospective chart review study, 50 patients with ptosis candidates for lower face correction were included between October 2019 and February 2020. To perform correction of the jawline, jaw angle, and marionette lines, APTOS thread (LLN2GS) and ELLANSE M type were used through an innovative technique. The efficacy (6 and 12 months after the surgery) and safety (1, 6, and 8 weeks after the surgery) were assessed by two surgeons independently. Data were analyzed by SPSS ver. 22 for windows (IBM Inc.). Results: In this study, 50 patients (4 male and 46 female) with Mean ± SD age of 53.84 ± 10.79 years old (Range: 42 years) were included. Regarding the results, patients' level of satisfaction (improved to excellent levels) increased from 74% at 6 months after the surgery to 86% at 12 months after the surgery. Moreover, the level of satisfaction obtained from surgeons (improved to excellent levels) decreased from 96% to 86% at 6 and 12 months after the surgery, respectively. Based on the results, there were substantial and perfect agreements between the surgeon and the independent surgeon to evaluate the surgery efficacy of facial rejuvenation 6 and 12 months after the surgery. No side effects were reported 6 and 8 weeks after surgery. Conclusion: Regarding the results, due to rare complications, deep satisfaction, and short downtime, the correction of the lower face in combination with APTOS thread (LLN2G) and ELLANSE M type through our innovative technique be considered an efficient and safe treatment. [ABSTRACT FROM AUTHOR]

The phenotypes associated with MED12 pathogenic variants are diverse. Male patients usually have missense variants, but the effects of base substitutions on mRNA splicing have not been investigated. Here, we report a Japanese brother with intellectual disability, characteristic facial appearance with blepharophimosis, cleft palate, Fallot tetralogy, vesicoureteral reflux, and deafness. A known missense pathogenic variant was detected in MED12, NM&#95;005120.3:c.887G>A p.(Arg296Gln), and X-linked Ohdo syndrome was diagnosed in combination with their phenotype. mRNA splicing of MED12 was evaluated qualitatively and quantitatively using long-range PCR-based targeted RNA sequencing (reverse transcribed long amplicon sequencing), and it was shown that this missense variant simultaneously causes aberrant splicing of the 42-bp in-frame deletion in exon 7, r.847&#95;888del, which accounts for approximately 30% of the mRNAs in both siblings. The X chromosome inactivation study showed that the X chromosome carrying the mutant allele was 100% inactivated in the carrier mothers. mRNA level analysis is essential for the accurate interpretation of the effects of variants. In this case, the MED12 protein function may be reduced by more than just an amino acid substitution, resulting in the patients with the most severe phenotype of MED12-related syndrome in males., (© 2024 Wiley Periodicals LLC.)

The role of basement membraneAm J Ophthalmol0.557491289196823286Canalicular inflammation in ophthalmic cases of herpes zoster and herpes simplexAm J Ophthalmol0.55555555619652287Prevalence of ocular anomalies among school childrenAm J Ophthalmol0.5555555561960688Neodymium laser cyclocoagulationJAMA Ophthalmol0.554140127197310589Ocular echometry in the diagnosis of congenital glaucomaJAMA Ophthalmol0.55263157919826190The use of liquid silicone in retinal detachment surgeryJAMA Ophthalmol0.551252847196241491Uveitis and joint diseases. I. Surgical techniques and managementJAMA Ophthalmol0.678899083195722629Changing trends in intraocular lens implantationJAMA Ophthalmol0.67619047619898830Trabeculectomy. [Extracted from the article]

This case report discusses the ophthalmic complications of frontal sinus mucoceles and describes the favorable long‐term surgical outcomes of a combined endoscopic and upper‐lid skin crease drainage approach carried out jointly with otorhinolaryngology. A 47‐year‐old single mother presented to eye casualty with markedly swollen eyelids and visual acuity of 6/6 in the left eye, no perception of light in the right. Ophthalmic examination revealed right‐sided hypoglobus and proptosis with exposure keratopathy inferiorly. There was complete ophthalmoplegia in the right eye and a hemorrhagic optic disc visible on fundoscopy. CT orbit with contrast confirmed a diagnosis of giant frontal mucocele with orbital extension. The patient underwent mucocele drainage via a modified anterior orbitotomy approach and FESS (Functional Endoscopic Sinus Surgery) drainage performed jointly with otorhinolaryngology. Two weeks post‐operatively her proptosis was resolving and by three months she had regained full extraocular motility. As expected, vision was not restored in the right eye. At one year, the patient's upper lid skin crease scar was completely buried in the eyelid's natural contour, and repeat CT scanning confirmed no re‐stenosis or mucocele recurrence. This case demonstrates, that a multidisciplinary approach to far‐lateral frontal sinus mucoceles with orbital extension and ophthalmic complications which combines an upper lid skin crease incision with FESS drainage, allows adequate access to the frontal sinus while preserving cosmesis. [ABSTRACT FROM AUTHOR]

Drooping of the upper eyelid and eyebrow (ptosis) is common among people and cause the patients dissatisfaction. Various methods have been developed to treatment of the upper eyelid and eyebrow ptosis. However, the current methods focus on surgery to improve the disorder. But patients are worried about the risks of the procedure, and seeking for a non‐invasive alternative method. Therefore, non‐invasive methods with consistent efficient improvement are needed, especially for middle‐aged patients. This study was conducted of 9 patients who underwent the upper eyelid and eyebrow ptosis. Endolift laser method was used to treat the patients' upper eyelid and eyebrow ptosis. The biometric assessment was used to evaluate the efficiency of the technique. Also the results were evaluated by 3 board‐certified dermatologists (blind). Additionally, patients' satisfaction was evaluated at the end of the treatment. The biometric results showed that Endolift laser can increase the thickness, density, and elasticity of the skin in the eyelid area. The patient's satisfaction results showed excellent improvement in the 90% of patients. The results by the dermatologist displayed improvement in about 90% of patient. Endolift laser has been proved efficient and consistent for upper eyelid and eyebrow ptosis rejuvenation and treatment. [ABSTRACT FROM AUTHOR]

Cell pyroptosis has received increased attention due to the associations between innate immunity and disease, and it has become a major focal point recently due to in‐depth studies of cancer. With increased research on pyroptosis, scientists have discovered that it has an essential role in viral infections, especially in the occurrence and development of some picornavirus infections. Many picornaviruses, including Coxsackievirus, a71 enterovirus, human rhinovirus, encephalomyocarditis virus, and foot‐and‐mouth disease virus induce pyroptosis to varying degrees. This review summarized the mechanisms by which these viruses induce cell pyroptosis, which can be an effective defense against pathogen infection. However, excessive inflammasome activation or pyroptosis also can damage the host's health or aggravate disease progression. Careful approaches that acknowledge this dual effect will aid in the exploration of picornavirus infections and the mechanisms that produce the inflammatory response. This information will promote the development of drugs that can inhibit cell pyroptosis and provide new avenues for future clinical treatment. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a highly heterogeneous malignancy, characterized by high mortality and poor prognosis. Ferroptosis is a newly defined nonapoptotic programmed cell death mechanism that has been implicated in the development of various pathological conditions. We aimed to identify ferroptosis‐related long noncoding RNA (lncRNAs) that might be used to predict GC prognosis. The data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. Two subtypes, C1 and C2, were identified, which had significant variations in prognosis and immune cell infiltrations. Differentially expressed genes between the subtypes were found to be involved in multiple tumor‐associated pathways. Subsequently, a training dataset and a testing dataset were created from the TCGA dataset. A predictive model for GC patients based on six ferroptosis‐related lncRNAs (including STX18‐AS1, MIR99AHG, LINC01197, LINC00968, LINC00865, and LEF1‐AS1) was developed. The model could stratify patients into a high‐ and low‐risk group, showing good predictive performance. The testing dataset, entire TCGA dataset, and GSE62254 cohort both confirmed the predictive value of the model. Compared to the clinical parameters (including gender, age, and grade), the risk model was an independent risk factor for GC patients. Moreover, a nomogram (containing our risk score model and clinical parameters) was constructed, which might provide great potential to improve prediction accuracy. Moreover, the single‐sample gene set enrichment analysis revealed that the high‐risk group was linked to various signaling pathways involved in the regulation of GC progression. Conclusively, a novel classification and risk model based on ferroptosis‐related lncRNAs that can predict oncologic outcomes for GC patients has been developed. [ABSTRACT FROM AUTHOR]

Background: Hypoxia and ferroptosis are crucial in the occurrence and development of hepatocellular carcinoma (HCC), and they both affect the immune status of the tumor microenvironment. Previous studies have also shown a link between hypoxia and ferroptosis. Patients and methods: In all, 814 HCC cases from The Cancer Genome Atlas and Gene Expression Omnibus databases were used as the discovery cohort, and 230 HCC cases from the International Cancer Genome Consortium database were used as the validation cohort. Hypoxia subtypes and ferroptosis subtypes were identified by consensus cluster analysis according to 174 hypoxia‐related genes and 193 ferroptosis‐related genes. The prognostic signature was constructed using the Cox and LASSO regression analyses, and two risk groups were identified. A comprehensive analysis of the clinical and immune characteristics between the two risk groups was further performed. Results: Two hypoxia subtypes and two ferroptosis subtypes were distinguished and verified; subsequently, a five‐gene prognostic signature was constructed and the risk score could be acquired by the following formula: risk score = 0.0604*Expression (CA9)−0.0714*Expression (ANXA10) + 0.1501*Expression (CDC20)−0.0853*Expression (CYP7A1) + 0.0530*Expression (SPP1). Compared with the low‐risk group, the high‐risk group had a worse prognosis. The high‐risk group also showed a higher level of immune infiltration than the low‐risk group, and immune checkpoints were generally upregulated in the high‐risk group. The antigen presentation ability of the low‐risk group was poor, which may be related to the immune escape mechanism. Drug sensitivity analysis indicated that the high‐ and low‐risk groups were sensitive to tyrosine kinase inhibitors and chemotherapeutic drugs, respectively. Conclusion: The hypoxia‐, ferroptosis‐, and immune‐associated prognostic signature we constructed could stratify patients with HCC and guide precise treatment. [ABSTRACT FROM AUTHOR]

The exact pathogenicity of cortactin in MG has not been elucidated, but it does support the diagnosis of immune-mediated MG.[5] Collagen Q antibodies have been reported in 3.3% (5/149) of tSN-MG patients and in 2.6% (7/266) of seropositive patients. The sera of tSN-MG patients may be tested for the above antibodies to assist in diagnosis, but these tests are not readily available. Confirming the diagnosis of juvenile ocular myasthenia gravis (OMG) is often difficult even after performing diagnostic tests, even more in triple seronegative cases and in such cases clinical judgement and response to immunotherapy can help in diagnosing. [Extracted from the article]