• Clostridioides difficile
• Clostridioides difficile toxin A
• Clostridioides difficile toxin B
• apoptosis
• calcium
• cell death
• cytotoxicity
• necrosis
• pore-forming toxins
• pyroptosis

• Clostridioides difficile infection
• Clostridioides difficile toxin B
• cellular senescence
• colorectal cancer
• inflammatory bowel diseases
• irritable bowel syndrome
• senescence-associated secretory phenotype

Clostridioides difficile (C. difficile) is progressively colonizing humans and animals living with humans. During this process, hypervirulent strains and mutated toxin A and B of C. difficile (TcdA and TcdB) are originating and developing. While in healthy subjects colonization by C. difficile becomes a risk after the use of antibiotics that alter the microbiome, other categories of people are more susceptible to infection and at risk of relapse, such as those with inflammatory bowel disease (IBD). Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma (CKs). Therefore, in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C. difficile infection and its progression and relapses. TcdB is internalized in the cell via three receptors: chondroitin sulphate proteoglycan 4; poliovirus receptor-like 3; and Wnt receptor frizzled family. Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types, while poliovirus receptor-like 3 induces only necrosis. It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis. Therefore, in subjects with IBD there are the conditions: (1) For greater susceptibility to C. difficile infection, such as the inflammatory state, and abnormalities of the microbiome and of the immune system; (2) for the enhancement of the cytotoxic activity of TcdB +Cks; and (3) for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis. The only therapeutic approach currently possible in IBD patients is monitoring of C. difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins. The future perspective is to generate bacteriophages against C. difficile for targeted therapy.

• Inflammatory bowel diseases
• Clostridioides difficile infection
• Cytokines
• Tumor necrosis factor-alpha
• Interferon-gamma
• Necrosis
• Apoptosis
• Cytotoxic synergism

• Animals
• Humans
• Antineoplastic Agents
• Bacterial Proteins/metabolism
• Bacterial Toxins
• Clostridioides difficile
• Clostridium Infections
• Cytokines/metabolism
• Enterotoxins
• Inflammatory Bowel Diseases/drug therapy
• Interferon-gamma/metabolism
• Necrosis
• Receptors, Wnt/metabolism
• Tumor Necrosis Factor-alpha/metabolism

Recent advances in molecular genetics have expanded our understanding of ovarian cancer. High levels of reactive oxygen species (ROS) and upregulation of antioxidant genes are common characteristic features of human cancers. This review reconsiders novel therapeutic strategies for ovarian cancer by focusing on redox homeostasis. A literature search was performed for preclinical and clinical studies published between January 1998 and October 2021 in the PubMed database using a combination of specific terms. ROS serves a central role in tumor suppression and progression by inducing DNA damage and mutations, genomic instability, and aberrant anti- and pro-tumorigenic signaling. Cancer cells increase their antioxidant capacity to neutralize the extra ROS. Additionally, antioxidants, such as CD44 variant isoform 9 (CD44v9) and nuclear factor erythroid 2-related factor 2 (Nrf2), mediate redox homeostasis in ovarian cancer. Furthermore, studies conducted on different cancer types revealed the dual role of antioxidants in tumor progression and inhibition. However, in animal models, genetic loss of antioxidant capacity in the host cannot block cancer initiation and progression. Host-derived antioxidant systems are essential to suppress carcinogenesis, suggesting that antioxidants serve a pivotal role in suppressing cancer development. By contrast, antioxidant activation in cancer cells confers aggressive phenotypes. Antioxidant inhibitors can promote cancer cell death by enhancing ROS levels. Concurrent inhibition of CD44v9 and Nrf2 may trigger apoptosis induction, potentiate chemosensitivity and enhance antitumor activities through the ROS-activated p38/p21 pathway. Antioxidants may have tumor-promoting and -suppressive functions. Therefore, an improved understanding of the role of antioxidants in redox homeostasis and developing antioxidant-specific inhibitors is necessary for treating ovarian cancer.

• CD44 variant isoform 9
• antioxidant
• nuclear factor erythroid 2-related factor 2
• ovarian cancer
• oxidative stress

• Cerebral ischemia reperfusion injury
• Fingolimod
• Inflammation
• NF-κB pathway
• p38 MAPK pathway

Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes.

In this study, the highly monodisperse hollow CeO₂ nanoparticles (H-CeO₂) with uniform morphology were obtained by in situ growing CeO₂ on solid silica nanoparticles and subsequently removing the silica core. The H-CeO₂ was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO₂-PEG.

The H-CeO₂-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1β, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO₂-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis.

This study reveals the therapeutic effects of CeO₂-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.

• MAPK signalling pathway
• ROS
• colitis
• hollow CeO2
• inflammation

• Clostridioides difficile
• apoptosis
• colonization
• endemy
• molecular strategy
• proinflammatory cytokine
• senescence
• toxins

• Clostridium difficile
• Mitochondrial function, apoptosis
• TcdA
• gC1qR

Esophageal squamous cell carcinoma (ESCC) is a worldwide concern. This study looked at the relationship between the expression of differential proteins and the clinicopathological data and survival rate of ESCC patients to identify potential tumor markers for the growth and metastasis of ESCC.

This study included 162 patients who underwent surgical excision for management of ESCC. Fresh ESCC tissue and adjacent normal tissue specimens were collected. Protein expressions were detected by western blotting. The expression of Hsp27 and P38MAPK were detected by immunohistochemistry in formalin-fixed paraffin embedded primary tissue specimens.

The rate of positive Hsp27 and P38MAPK expression in ESCC tissue were higher than in normal esophageal tissue (p<0.05). The expression of P38MAPK was related to the depth of infiltration (p<0.05). The expression of Hsp27 was correlated with lymph node metastasis (p<0.05), but not with age, depth of infiltration, or tumor size. ROC were plotted to estimate the significance of the diagnosis: for Hsp27, AUC=0.735 (p<0.05), for P38MAPK, AUC=0.882 (p<0.05).

The expression of Hsp27 and P38MAPK plays a role in ESCC development. Hsp27 and P38MAPK could be used as prognostic factors in ESCC.