Multiple sclerosis (MS) is a heterogenous autoimmune-mediated disease of the central nervous system (CNS) characterized by inflammation, demyelination and chronic progressive neurodegeneration. Among its broad and unpredictable range of neuropsychiatric symptoms, behavioral changes are common, even from the early stages of the disease, while they are associated with cognitive deficits in advanced MS. According to DSM-5, behavioral disorders include attention deficits, oppositional, defiant and conduct disorders, anxiety, panic, obsessive-compulsive disorders (OCD), disruptive and emotional disorders, while others include also irritability, agitation, aggression and executive dysfunctions. Approximately 30 to 80% of individuals with MS demonstrate behavioral changes associated with disease progression. They are often combined with depression and other neuropsychiatric disorders, but usually not correlated with motor deficits, suggesting different pathomechanisms. These and other alterations contribute to disability in MS. While no specific neuropathological data for behavioral changes in MS are available, those in demyelination animal models share similarities with white matter and neuroinflammatory abnormalities in humans. Neuroimaging revealed prefrontal cortical atrophy, interhemispheric inhibition and disruption of fronto-striato-thalamic and frontoparietal networks. This indicates multi-regional patterns of cerebral disturbances within the MS pathology although their pathogenic mechanisms await further elucidation. Benefits of social, psychological, behavioral interventions and exercise were reported. Based on systematical analysis of PubMed, Google Scholar and Cochrane library, current epidemiological, clinical, neuroimaging and pathogenetic evidence are reviewed that may aid early identification of behavioral symptoms in MS, and promote new therapeutic targets and strategies.

Skin malignant melanoma (MM) is one of the most frequent and aggressive neoplasia worldwide. Its associated high mortality rates are mostly due to its metastases, while diagnosis and treatment of MM in its early stages is of favorable prognostic. Even skin superficial MMs at incipient local stages can already present with lymph node invasion and distant metastases. Therefore, knowledge of the controllable risk factors and pathogenic mechanisms of MM development, spreading, and metastatic pattern, as well as early diagnosis, are essential to decrease the high mortality rates associated with cutaneous malignant melanoma. Genetic factors are incriminated, although lifetime-acquired genetic mutations appear to be even more frequently involved in the development of MM. Skin melanocytes divide only twice per year and have time to accumulate genetic mutations as a consequence of environmental aggressive factors, such as UV exposure. In the search for more promising therapies, matrix metalloproteinases have become of significant interest, such as MMP-1, MMP-2, MMP-9, and MMP-13, which have been linked to more aggressive forms of cancer and earlier metastases. Therefore, the development of specific synthetic inhibitors of MMP secretion or activity could represent a more promising and effective approach to the personalized treatment of MM patients.

Liver cancer is a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form, characterized by high incidence and mortality rates. Despite advances in targeted therapies and immunotherapies, the prognosis for advanced liver cancer remains poor. This underscores the urgent need for a deeper understanding of the molecular mechanisms underlying HCC to enable early detection and the development of novel therapeutic strategies. Post-translational modifications (PTMs) are crucial regulatory mechanisms in cellular biology, affecting protein functionality, interactions, and localization. These modifications, including phosphorylation, acetylation, methylation, ubiquitination, and glycosylation, occur after protein synthesis and play vital roles in various cellular processes. Recent advances in proteomics and molecular biology have highlighted the complex networks of PTMs, emphasizing their critical role in maintaining cellular homeostasis and disease pathogenesis. Dysregulation of PTMs has been associated with several malignant cellular processes in HCC, such as altered cell proliferation, migration, immune evasion, and metabolic reprogramming, contributing to tumor growth and metastasis. This review aims to provide a comprehensive understanding of the pathological mechanisms and clinical implications of various PTMs in liver cancer. By exploring the multifaceted interactions of PTMs and their impact on liver cancer progression, we highlight the potential of PTMs as biomarkers and therapeutic targets. The significance of this review lies in its potential to inform the development of novel therapeutic approaches and improve prognostic tools for early intervention in the fight against liver cancer.

Osteonecrosis of the femoral head (ONFH) is a condition that causes considerable pain and discomfort for patients, and its pathogenic mechanisms are not yet fully understood. While there have been many studies that suggest multiple factors may contribute to its development, current treatments involve both surgical and nonsurgical options. However, there is still much room for improvement in these treatment methods, particularly when it comes to preventing postoperative complications and optimizing surgical procedures. Nanomaterials, as a type of small molecule material, have shown great promise in treating bone tissue diseases, including ONFH. In fact, several nanocomposite materials have demonstrated specific effects in preventing ONFH, promoting bone tissue repair and growth, and optimizing surgical treatment. This article provides a comprehensive overview of current treatments for ONFH, including their advantages and limitations, and reviews the latest advances in nanomaterials for treating this condition. Additionally, this article explores the therapeutic mechanisms involved in using nanomaterials to treat ONFH and to identify new methods and ideas for improving outcomes for patients.

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

BACKGROUND: A growing body of research has shown that patients with coronavirus disease 2019 (COVID-19) have significantly higher rates of venous thromboembolism (VTE) than healthy. However, the mechanism remains incompletely elucidated. This study aimed to further investigate the molecular mechanisms underlying the development of this complication.
METHODS: The gene expression profiles of COVID-19 and VTE were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for COVID-19 and VTE, functional annotation, a protein-protein interactions (PPI) network, module construction, and hub gene identification were performed. Finally, we constructed a transcription factor (TF)-gene regulatory network and a TF-miRNA regulatory network for hub genes.
RESULTS: A total of 42 common DEGs were selected for subsequent analyses. Functional analyses showed that biological function and signaling pathways collectively participated in the development and progression of VTE and COVID-19. Finally, 8 significant hub genes were identified using the cytoHubba plugin, including RSL24D1, RPS17, RPS27, HINT1, COX7C, RPL35, RPL34, and NDUFA4, which had preferable values as diagnostic markers for COVID-19 and VTE.
CONCLUSIONS: Our study revealed the common pathogenesis of COVID-19 and VTE. These common pathways and pivotal genes may provide new ideas for further mechanistic studies.

BACKGROUND: Alzheimer\'s disease (AD) is a complicated neurodegenerative disease with cognitive impairment occurring in the older people, in which extracellular accumulation of β-amyloid and intracellular aggregation of hyperphosphorylated tau are regarded as the prevailing theories. However, the exact AD mechanism has not been determined. Moreover, there is no effective treatment available in phase III trials to eradicate AD, which is imperative to explore novel treatments.
OBJECTIVE: A number of up-to-date pre-clinical studies on cognitive impairment is beneficial to clarify the pathology of AD. This review recapitulates several advances in AD pathobiology and discusses the neuroprotective effects of natural compounds, such as phenolic compounds, natural polysaccharides and oligosaccharides, peptide, and lipids, underscoring the therapeutic potential for AD.
METHODS: Electronic databases involving PubMed, Web of Science, and Google Scholar were searched up to October 2023. Articles were conducted using the keywords like Alzheimer\'s disease, pathogenic mechanisms, natural compounds, and neuroprotection.
RESULTS: This review summarized several AD pathologies and the neuroprotective effects of natural compounds such as natural polysaccharides and oligosaccharides, peptide, and lipids.
CONCLUSIONS: We have discussed the pathogenic mechanisms of AD and the effect natural products on neurodegenerative diseases particularly in treating AD. Specifically, we investigated the molecular pathways and links between natural compounds and Alzheimer\'s disease such as through NF-κB, Nrf2, and mTOR pathway. Further investigation is necessary in exploring the bioactivity and effectiveness of natural compounds in clinical trials, which may provide a promising treatment for AD patients.

Arrhythmogenic cardiomyopathy (ACM) is a rare genetic cardiac disease characterized by the progressive substitution of myocardium with fibro-fatty tissue. Clinically, ACM shows wide variability among patients; symptoms can include syncope and ventricular tachycardia but also sudden death, with the latter often being its sole manifestation. Approximately half of ACM patients have been found with variations in one or more genes encoding cardiac intercalated discs proteins; the most involved genes are plakophilin 2 (PKP2), desmoglein 2 (DSG2), and desmoplakin (DSP). Cardiac intercalated discs provide mechanical and electro-metabolic coupling among cardiomyocytes. Mechanical communication is guaranteed by the interaction of proteins of desmosomes and adheren junctions in the so-called area composita, whereas electro-metabolic coupling between adjacent cardiac cells depends on gap junctions. Although ACM has been first described almost thirty years ago, the pathogenic mechanism(s) leading to its development are still only partially known. Several studies with different animal models point to the involvement of the Wnt/β-catenin signaling in combination with the Hippo pathway. Here, we present an overview about the existing murine models of ACM harboring variants in intercalated disc components with a particular focus on the underlying pathogenic mechanisms. Prospectively, mechanistic insights into the disease pathogenesis will lead to the development of effective targeted therapies for ACM.

Human Ureaplasma species are being increasingly recognized as opportunistic pathogens in human genitourinary tract infections, infertility, adverse pregnancy, neonatal morbidities, and other adult invasive infections. Although some general reviews have focused on the detection and clinical manifestations of Ureaplasma spp., the molecular epidemiology, antimicrobial resistance, and pathogenesis of Ureaplasma spp. have not been adequately explained. The purpose of this review is to offer valuable insights into the current understanding and future research perspectives of the molecular epidemiology, antimicrobial resistance, and pathogenesis of human Ureaplasma infections. This review summarizes the conventional culture and detection methods and the latest molecular identification technologies for Ureaplasma spp. We also reviewed the global prevalence and mechanisms of antibiotic resistance for Ureaplasma spp. Aside from regular antibiotics, novel antibiotics with outstanding in vitro antimicrobial activity against Ureaplasma spp. are described. Furthermore, we discussed the pathogenic mechanisms of Ureaplasma spp., including adhesion, proinflammatory effects, cytotoxicity, and immune escape effects, from the perspectives of pathology, related molecules, and genetics.

Multiple sclerosis (MS) is an autoimmune-mediated disease of the central nervous system characterized by inflammation, demyelination and chronic progressive neurodegeneration. Among its broad and unpredictable range of clinical symptoms, cognitive impairment (CI) is a common and disabling feature greatly affecting the patients\' quality of life. Its prevalence is 20% up to 88% with a wide variety depending on the phenotype of MS, with highest frequency and severity in primary progressive MS. Involving different cognitive domains, CI is often associated with depression and other neuropsychiatric symptoms, but usually not correlated with motor and other deficits, suggesting different pathophysiological mechanisms. While no specific neuropathological data for CI in MS are available, modern research has provided evidence that it arises from the disease-specific brain alterations. Multimodal neuroimaging, besides structural changes of cortical and deep subcortical gray and white matter, exhibited dysfunction of fronto-parietal, thalamo-hippocampal, default mode and cognition-related networks, disruption of inter-network connections and involvement of the γ-aminobutyric acid (GABA) system. This provided a conceptual framework to explain how aberrant pathophysiological processes, including oxidative stress, mitochondrial dysfunction, autoimmune reactions and disruption of essential signaling pathways predict/cause specific disorders of cognition. CI in MS is related to multi-regional patterns of cerebral disturbances, although its complex pathogenic mechanisms await further elucidation. This article, based on systematic analysis of PubMed, Google Scholar and Cochrane Library, reviews current epidemiological, clinical, neuroimaging and pathogenetic evidence that could aid early identification of CI in MS and inform about new therapeutic targets and strategies.