Autophagy modulation in cancer therapy: Challenges coexist with opportunities.

Autophagy, a crucial intracellular degradation process facilitated by lysosomes, plays a pivotal role in maintaining cellular homeostasis. The elucidation of autophagy key genes and signaling pathways has significantly advanced our understanding of this process and has led to the exploration of autophagy as a promising therapeutic approach. This review comprehensively assesses the latest developments in small molecule modulators targeting autophagy.

Small molecule inhibitors targeting mA regulators.

As the most common form of epigenetic regulation by RNA, N methyladenosine (mA) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between mA and cancers has garnered substantial attention in recent years.

Natural products and derivatives for breast cancer treatment: From drug discovery to molecular mechanism.

Background: Breast cancer stands as the most common malignancy among women globally and a leading cause of cancer-related mortality. Conventional treatments, such as surgery, hormone therapy, radiotherapy, chemotherapy, and small-molecule targeted therapy, often fall short of addressing the complexity and heterogeneity of certain breast cancer subtypes, leading to drug resistance and metastatic progression. Thus, the search for novel therapeutic targets and agents is imperative.

Structure-Guided Discovery and Preclinical Assessment of Novel (Thiophen-3-yl)aminopyrimidine Derivatives as Potent ERK1/2 Inhibitors.

The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit In preclinical studies, showed powerful ERK1/2 inhibitory activities (ERK1/2 IC = 0.

Appraising the quality standard of clinical practice guidelines related to central venous catheter-related thrombosis prevention: a systematic review of clinical practice guidelines.

Objective: To evaluate the quality and analyse the content of clinical practice guidelines regarding central venous catheter-related thrombosis (CRT) to provide evidence for formulating an evidence-based practice protocol and a risk assessment scale to prevent it.

Design: Scoring and analysis of the guidelines using the AGREE II and AGREE REX scales.

Data Sources: Pubmed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and the Chinese Biomedical Literature, and the relevant websites of the guideline, were searched from 1 January 2017 to 26 March 2022.

Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives.

Eukaryotic cells engage in autophagy, an internal process of self-degradation through lysosomes. Autophagy can be classified as selective or non-selective depending on the way it chooses to degrade substrates. During the process of selective autophagy, damaged and/or redundant organelles like mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes, and lipid droplets are selectively recycled.

Targeted regulated cell death with small molecule compounds in colorectal cancer: Current perspectives of targeted therapy and molecular mechanisms.

Colorectal cancer (CRC), a tumor of the digestive system, is characterized by high malignancy and poor prognosis. Currently, targeted therapy of CRC is far away from satisfying. The molecular mechanisms of regulated cell death (RCD) have been clearly elucidated, which can be intervened by drug or genetic modification.

Quercetin ameliorates ferroptosis of rat cardiomyocytes via activation of the SIRT1/p53/SLC7A11 signaling pathway to alleviate sepsis‑induced cardiomyopathy.

Sepsis‑induced cardiomyopathy (SIC) is a manifestation of multiple organ failure as a result of sepsis and is a serious threat to life. Here, the effect and mechanisms of quercetin (QUE) in SIC were assessed. It was found that patients with SIC expressed lower serum levels of glutathione peroxidase 4 (GPX4) and SIRT1 but higher levels of CK‑MB, cTnI, TNF‑α, and IL‑6 compared with healthy individuals.

Targeted therapy for non-small-cell lung cancer: New insights into regulated cell death combined with immunotherapy.

Non-small-cell lung cancer (NSCLC), which has a high rate of metastatic spread and drug resistance, is the most common subtype of lung cancer. Therefore, NSCLC patients have a very poor prognosis and a very low chance of survival. Human cancers are closely linked to regulated cell death (RCD), such as apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis.

Quercetin inhibits the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve sepsis-induced cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) has high morbidity and mortality. Quercetin (QUE) has been used to treat many inflammatory diseases related to pyroptosis. However, its effect on SIC has not been reported before.

Discovery of Novel Indazole Chemotypes as Isoform-Selective JNK3 Inhibitors for the Treatment of Parkinson's Disease.

c-Jun N-terminal kinases (JNKs) are involved in the pathogenesis of various diseases. In particular, JNK3 and not JNK1/2 is primarily expressed in the brain and plays a key role in mediating neurodegenerative diseases like Parkinson's disease (PD). Due to the sequence similarity of JNK isoforms, developing isoform-selective JNK3 inhibitors to evaluate their biological functions and therapeutic potential in PD has become a challenge.

Recent advances of β-catenin small molecule inhibitors for cancer therapy: Current development and future perspectives.

The Wnt/β-catenin signaling pathway is involved in many cellular physiological processes, including embryonic development, cell proliferation and differentiation, tissue homeostasis and regeneration, etc. Aberrant activation of Wnt/β-catenin signaling is one of the most typical features in the development and progression of cancer. Abnormal accumulation of β-catenin, a core component of the Wnt/β-catenin signaling pathway, is one of the main factors leading to abnormal activation of the Wnt/β-catenin signaling pathway.

Exposure effects of inhaled nickel nanoparticles on the male reproductive system via mitochondria damage.

Nickel nanoparticles (Ni NPs) have a wide range of application prospects, however there is still a lack of their safety evaluation for the reproductive system. Nowadays, male reproductive health has been widely concerned for the increasing incidence of male infertility. To investigate the male reproductive toxicity induced by Ni NPs and its relation with the mitochondrial fission and mitophagy, male mice were administered with or without 5, 15, and 45 mg/kg of Ni NPs by intratracheal instillation.

Factors Influencing Post-Stroke Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

Objective: Type 2 diabetes mellitus (T2DM) and ischemic stroke, which are common diseases among older people, are closely related to cognitive impairment. This study aims to investigate the influencing factors of post-stroke cognitive impairment (PSCI) in patients with T2DM.

Methods: We enrolled 161 patients with T2DM who experienced acute ischemic stroke and were hospitalized in the Department of Neurology, Jinan Central Hospital, Shandong, China.

Unraveling the Design and Discovery of c-Jun N-Terminal Kinase Inhibitors and Their Therapeutic Potential in Human Diseases.

c-Jun N-terminal kinases (JNKs), members of the mitogen-activated protein kinase (MAPK) family, are encoded by three genes: , , and . JNKs are involved in the pathogenesis and development of many diseases, such as neurodegenerative diseases, inflammation, and cancers. Therefore, JNKs have become important therapeutic targets.

Study of the mechanism of mitochondrial division and mitochondrial autophagy in the male reproductive toxicity induced by nickel nanoparticles.

Male reproductive health is deteriorating, and fertility is largely affected by environmental factors. This study aims to investigate the potential mechanism underlying mitochondrial division and mitochondrial autophagy in the male reproductive toxicity of nickel nanoparticles (Ni NPs). An mouse (BALB/c) model was constructed to calculate testicular organ coefficients and sperm abnormality rates, and detect serum reproductive hormones, testicular pathological morphology, and the expression of Drp1, Pink1, and Parkin proteins.

Intermittent exposure to airborne particulate matter induces subcellular dysfunction and aortic cell damage in BALB/c mice through multi-endpoint assessment at environmentally relevant concentrations.

Airborne particulate matter (PM) has been linked to cardiovascular diseases, but the underlying mechanisms remain unclear, especially at realistic exposure levels. In this study, both male and female BALB/c mice were employed to assess vascular homeostasis following a standard urban particulate matter, PM SRM1648a, via oropharyngeal aspiration at three environmentally relevant concentrations. The tested indicators included histopathological observation and lipid deposition, as well as redox biology and inflammatory responses.

Mechanisms underlying reproductive toxicity induced by nickel nanoparticles identified by comprehensive gene expression analysis in GC-1 spg cells.

The public around the world is increasingly concerned about male reproductive health. The impact of nickel nanoparticles (Ni NPs) on male reproductive toxicity including sperm production, motility and fertilizing capacity has been confirmed by our previous researches. In the current study of Ni NPs-inducing toxicity, the expression profiles of piRNAs and their predicted target genes associated with male infertility, were obtained.

Effect and mechanism of PI3K/AKT/mTOR signaling pathway in the apoptosis of GC-1 cells induced by nickel nanoparticles.

Nickel nanoparticles (Ni NPs) have a wide range of application prospects, but there is still a lack of their safety evaluation for the reproductive system. Nowadays, male reproductive health has been widely concerned because of the increasing incidence of male infertility. Studies have shown that Ni NPs can cause male reproductive toxicity.

Advance on toxicity of metal nickel nanoparticles.

As a kind of conventional metal nanomaterial, nickel nanoparticles (Ni NPs) have broad application prospects in the fields of magnetism, energy technology and biomedicine and have quickly attracted great interest. The potential negative effects of Ni NPs have also attracted wide attention from some researchers. Studies have shown that Ni NPs cause a variety of toxic effects on cells, animals and humans and have toxic effects of multiple systems such as respiratory system, cardiovascular system and reproductive system.

Molecular mechanisms underlying nickel nanoparticle induced rat Sertoli-germ cells apoptosis.

This study was done on SD rat Sertoli-germ co-cultured cells (Sertoli-germ cells) with nickel nanoparticles (Ni NPs). A series of investigations were performed to observe the role of Ni NPs on the apoptosis of Sertoli-germ cells and to explore the long-chain non-coding RNA (lncRNA) functions on key signaling pathways and regulatory mechanisms. We found that Ni NPs had an apoptotic effect on Sertoli-germ cells.

Study on the damage of sperm induced by nickel nanoparticle exposure.

As a new type of nanomaterials, nickel nanoparticles (Ni NPs) have been widely used by human beings, whose exposure probability was greatly increasing. Many studies have shown that Ni NPs can induce apoptosis, oxidative stress and DNA damage. Nowadays, male reproductive health is an important public health problem, which is a hot topic in toxicological research.