preservation damage

PURPOSE OF REVIEW: Tafamidis is currently the only approved disease-modifying treatment for ATTR-CM. However, there have been important developments in the treatment of ATTR-CM, as the results of two phase 3 trials were published and several other trials are in their final stages. In this review, we summarize current and future therapies for ATTR-CM. RECENT FINDINGS: Recently, acoramidis, a TTR stabilizer has been proven to be effective in reducing mortality and morbidity compared to placebo in the ATTRibute-CM trial...

PURPOSE: Benzalkonium chloride (BAK) is a common preservative in ophthalmic formulations that causes cytotoxic damage to the corneal epithelial cells. This study aims to explore the role of mesenchymal stem cell (MSC)-derived conditioned medium in modulating the BAK-induced cytotoxic effects in cultured human corneal epithelial cells (HCECs) as a cell-free therapeutic agent. METHODS: The in vitro cultured HCECs derived from a HCE cell line were treated with BAK (0...

Introduction: Recent advances have enabled organotypic culture of beating human myocardial slices that are stable for weeks. However, human myocardial samples are rare, exhibit high variability and frequently originate from diseased hearts. Thus, there is a need to adapt long-term slice culture for animal myocardium. When applied to animal cardiac slices, studies in healthy or genetically modified myocardium will be possible. We present the culture of slices from rabbit hearts, which resemble the human heart in microstructure, electrophysiology and excitation-contraction coupling...

BACKGROUND: Muscle atrophy is a common consequence of the loss of innervation and is accompanied by mitochondrial dysfunction. Mitophagy is the adaptive process through which damaged mitochondria are removed via the lysosomes, which are regulated in part by the transcription factor TFE3. The role of lysosomes and TFE3 are poorly understood in muscle atrophy, and the effect of biological sex is widely underreported. METHODS: Wild-type (WT) mice, along with mice lacking TFE3 (KO), a transcriptional regulator of lysosomal and autophagy-related genes, were subjected to unilateral sciatic nerve denervation for up to 7 days, while the contralateral limb was sham-operated and served as an internal control...

OBJECTIVE: During radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequelae, which dramatically affect women's quality of life because of urinary, anorectal, and sexual postoperative dysfunctions.1 , 2 Direct visualization is one way to preserve hypogastric nerves(HNs), pelvic splanchnic nerves(PSNs), and the bladder branches from the inferior hypogastric plexus(IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers...

PURPOSE: The definitive treatment for chronic suppurative otitis media is surgery. Surgical technique and procedure varies according to individual case findings and pathology and may require mastoidectomies in which the canal wall is preserved or lowered to eradicate disease from mastoid air cells. Surgical treatment of chronic middle ear disease carries a risk of damage to the inner ear. The aim of this study was to investigate whether the noise produced by the tour system following chronic ear surgery causes sensorineural hearing loss, a condition for which not many studies have been published in the literature...

BACKGROUND: Mercury chloride (HgCl2 ) damages tissues it comes in contact with in sufficient concentration. This study evaluated the protective effects of n-butanol fraction of Phoenix dactylifera (BFPD) on mercury-triggered liver toxicity in Wistar rats. 25 male rats were divided into 5 groups of 5 rats each. Group I was administered 2 ml/kg of distilled water; group II was administered 5 mg/kg of HgCl2 ; group III was administered 500 mg/kg of BFPD + 5 mg/kg of HgCl2 ; group IV was administered 1000 mg/kg of BFPD + 5 mg/kg of HgCl2 , while group V was administered 100 mg/kg of silymarin + 5 mg/kg of HgCl2 ...

Preserving the genomic integrity stands a fundamental necessity, primarily achieved by the DNA repair proteins through their continuous patrolling on the DNA in search of lesions. However, comprehending how even a single base-pair lesion can be swiftly and specifically recognized amidst millions of base-pair sites remains a formidable challenge. In this study, we employ extensive molecular dynamics simulations using an appropriately tuned model of both protein and DNA to probe the underlying molecular principles...

BACKGROUND AND OBJECTIVE: Mechanical ventilation is a life-saving treatment for critically-ill patients. During treatment, patient-ventilator asynchrony (PVA) can occur, which can lead to pulmonary damage, complications, and higher mortality. While traditional detection methods for PVAs rely on visual inspection by clinicians, in recent years, machine learning models are being developed to detect PVAs automatically. However, training these models requires large labeled datasets, which are difficult to obtain, as labeling is a labour-intensive and time-consuming task, requiring clinical expertise...

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation...

Sickle cell disease (SCD) is a hereditary hemoglobinopathy marked by hemolytic anemia and vaso-occlusive events (VOE). Chronic endothelial activation, inflammation, and coagulation activation contribute to vascular congestion, VOE, and end-organ damage. Coagulation proteases like thrombin and activated protein C (APC) modulate inflammation and endothelial dysfunction by activating protease-activated receptor 1 (PAR1), a G-protein coupled receptor. Thrombin cleaves PAR1 at Arg41, while APC cleaves PAR1 at Arg46, initiating either pro-inflammatory or cytoprotective signaling, respectively, a signaling conundrum known as biased agonism...

OBJECTIVE: To explore and compare the current mainstream testicular tissue freezing methods, namely vitrification and controlled slow freezing, and optimize the best testicular tissue freezing methods. METHODS: Testicular tissues of 3-week-old mice and <2-year old prepubertal cynomophage monkeys were collected and cut to 6-26 mm3, and divided into three groups: Fresh group, vitrification group and controlled slow freezing group were resuscitated after 5-7 days of freezing...

BACKGROUND: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. METHODS: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II...

Aspergillus flavus colonization on agricultural products during preharvest and postharvest results in tremendous economic losses. Inspired by the synergistic antifungal effects of essential oils, the aims of this study were to explore the mechanism of combined cinnamaldehyde and nonanal (SCAN ) against A. flavus and to evaluate the antifungal activity of SCAN loading into diatomite (DM). Shriveled mycelia were observed by scanning electron microscopy, especially in the SCAN treatment group. Calcofluor white staining, transmission electron microscopy, dichloro-dihydro-fluorescein diacetate staining and the inhibition of key enzymes in tricarboxylic acid cycle indicated that the antifungal mechanism of SCAN against A...

Neuronal death resulting from ischemic stroke is the primary cause of adult mortality and disability, and effective neuroprotective agents for poststroke intervention are still lacking. Remote ischemic postconditioning (RIPostC) has demonstrated significant protective effects against ischemia in various organs; however, the specific mechanisms are not fully understood. This study investigated the potential neuroprotective mechanisms of RIPostC in the context of ischemic stroke. Using a rat model of middle cerebral artery occlusion, we found that RIPostC mitigated neurological damage, improved movement in the open-field test, and protected against neuronal apoptosis...

Cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene that encodes cystinosin, a ubiquitous lysosomal cystine/H+ antiporter. The hallmark of the disease is progressive accumulation of cystine and cystine crystals in virtually all tissues. At the kidney level, human cystinosis is characterized by the development of renal Fanconi syndrome and progressive glomerular and interstitial damage leading to end-stage kidney disease in the second or third decade of life. The exact molecular mechanisms involved in the pathogenesis of renal disease in cystinosis are incompletely elucidated...

MDC1 (Mediator of DNA damage Checkpoint protein 1) functions to facilitate the localization of numerous DNA damage response (DDR) components to DNA double-strand break sites. MDC1 is an integral component in preserving genomic stability and appropriate DDR regulation. There haven't been systematic investigations of MDC1 mutations that induce cancer and genomic instability. Variations in nsSNPs have the potential to modify the protein chemistry and their function. Describing functional SNPs in disease-associated genes presents a significant conundrum for investigators, it is possible to assess potential functional SNPs before conducting larger population examinations...

When cells proliferate, stress on DNA replication or exposure to endogenous or external insults frequently results in DNA damage. DNA-Damage Response (DDR) networks are complex signaling pathways used by multicellular organisms to prevent DNA damage. Depending on the type of broken DNA, the various pathways, Base-Excision Repair (BER), Nucleotide Excision Repair (NER), Mismatch Repair (MMR), Homologous Recombination (HR), Non-Homologous End-Joining (NHEJ), Interstrand Crosslink (ICL) repair, and other direct repair pathways, can be activated separately or in combination to repair DNA damage...

Calorie restriction is a nutritional intervention that reproducibly protects against the maladaptive consequences of cardiovascular diseases. Pathological cardiac hypertrophy leads to cellular growth, dysfunction (with mitochondrial dysregulation), and oxidative stress. The mechanisms behind the cardiovascular protective effects of calorie restriction are still under investigation. In this study, we show that this dietetic intervention prevents cardiac protein elevation, avoids fetal gene reprogramming (atrial natriuretic peptide), and blocks the increase in heart weight per tibia length index (HW/TL) seen in isoproterenol-induced cardiac hypertrophy...

The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention...