Microglia, as immune cells in the central nervous system, are closely related to cognitive impairment associated with type 2 diabetes (T2D). Preliminary explorations have investigated the relationship between T2D-related cognitive impairment and the activation and polarization of microglia. This review summarizes the potential mechanisms of microglial activation and polarization in the context of T2D. It discusses central inflammatory responses, neuronal apoptosis, amyloid-β deposition, and abnormal phosphorylation of Tau protein mediated by microglial activation and polarization, exploring the connections between microglial activation and polarization and T2D-related cognitive impairment from multiple perspectives. Additionally, this review provides references for future treatment targeting microglia in T2D-related cognitive impairment and for clinical translation.

Titanium and its alloys have been widely used in bone tissue defect treatment owing to their excellent comprehensive properties. However, because of the biological inertness of the surface, it is difficult to achieve satisfactory osseointegration with the surrounding bone tissue when implanted into the body. Meanwhile, an inflammatory response is inevitable, which leads to implantation failure. Therefore, solving these two problems has become a new research hotspot. In current studies, various surface modification methods were proposed to meet the clinical needs. Yet, these methods have not been classified as a system to guide the follow-up research. These methods are demanded to be summarized, analyzed, and compared. In this manuscript, the effect of physical signal regulation (multi-scale composite structure) and chemical signal regulation (bioactive substance) generated by surface modification in promoting osteogenesis and reducing inflammatory responses was generalized and discussed. Finally, from the perspective of material preparation and biocompatibility experiments, the development trend of surface modification in promoting titanium implant surface osteogenesis and anti-inflammatory research was proposed.

The immune system\'s role in maintaining the health of the gastrointestinal (GI) system is like a double-edged sword. Simultaneously, it could reduce the risk of pathogen invasion by the inflammatory response. However, if regulated improperly, it could also propagate oncogenic signaling that transfers a normal cell into the malignant counterpart. Thus, several mechanisms have been proposed, such as the immune system could disturb the GI homeostasis and increase the survival and proliferative capacity of cells, leading to the formation of a wide range of malignancies. Among the endless list of these mechanisms, inflammatory responses are currently fascinating research areas, as this response regulation is by the gut microbiota. Given this, microbiota manipulation might be a convenient and efficient way to prevent GI cancer. Probiotics could potentially achieve this by overturning the milieu in favor of normal gut homeostasis. In addition to the safety of the use of probiotics, along with their potential ability to interact with immune system responses, these bacteria are also being analyzed from the perspective of dietary supplements. In the present review, we aimed to look into the mechanisms through which probiotics modulate immune response to stimulate anti-inflammatory responses and promote immune surveillance against neoplastic cells.

Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4+ T/CD8+ T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3+ T,CD4+T and CD8+T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4+ and CD8+ T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.

Cyanobacteria (blue-green algae) have been present on Earth for over 2 billion years, and can produce a variety of bioactive molecules, such as cyanotoxins. Microcystins (MCs), the most frequently detected cyanotoxins, pose a threat to the aquatic environment and to human health. The classic toxic mechanism of MCs is the inhibition of the protein phosphatases 1 and 2A (PP1 and PP2A). Immunity is known as one of the most important physiological functions in the neuroendocrine-immune network to prevent infections and maintain internal homoeostasis in fish. The present review aimed to summarize existing papers, elaborate on the MC-induced immunotoxicity in fish, and put forward some suggestions for future research. The immunomodulatory effects of MCs in fish depend on the exposure concentrations, doses, time, and routes of exposure. Previous field and laboratory studies provided strong evidence of the associations between MC-induced immunotoxicity and fish death. In our review, we summarized that the immunotoxicity of MCs is primarily characterized by the inhibition of PP1 and PP2A, oxidative stress, immune cell damage, and inflammation, as well as apoptosis. The advances in fish immunoreaction upon encountering MCs will benefit the monitoring and prediction of fish health, helping to achieve an ecotoxicological goal and to ensure the sustainability of species. Future studies concerning MC-induced immunotoxicity should focus on adaptive immunity, the hormesis phenomenon and the synergistic effects of aquatic microbial pathogens.

MicroRNAs (miRNAs) perform a variety of important cellular functions, including regulating the cell cycle, apoptosis and differentiation, amongst others. Recent research has demonstrated an essential function performed by miRNAs in regulating pyroptosis, which is a type of programmed cell death associated with inflammatory responses that plays a critical role in numerous diseases. Through direct or indirect action on proteins associated with the pyroptosis signaling pathway, miRNAs are involved in the pathological processes of cardiovascular, kidney and immune diseases, among others. The present review discusses the maturation process of miRNAs and the process of pyroptosis, with a specific focus on the transport of miRNAs to damaged cells via exosomes, shedding vesicles and protein stabilized complexes, as well as the role of different miRNAs in the regulation of pyroptosis through different gene and protein targets. The aim of the present review was to provide a novel insight into the regulatory role of miRNAs in pyroptosis and new treatment options for pyroptosis‑associated diseases.

Osteoarthritis (OA) is the most common form of arthritis, for which treatment options are not always satisfactory, since complete cure for OA is not yet possible. A better understanding of OA pathogenesis is thus important. The peroxisome proliferator‑activated receptor (PPAR) plays a major regulatory role in lipid metabolism and energy homeostasis. This review article aimed to discuss the biological function of PPARs, and their role in regulating OA progression, as well as the therapeutic aspect of PPARs in OA. Studies indicate that PPARs regulate articular cartilage homeostasis through the modulation of various signaling pathways, and reduce the inflammatory responses in human OA cartilage. Furthermore, the deficiency of PPARs in the articular cartilage might be responsible for the acceleration of severe OA by increasing catabolic activity and suppression of chondroprotection. Therapeutic applications of PPAR‑agonists can thus reduce the development of cartilage lesions by inhibiting the synthesis of various catabolic and inflammatory factors involved in the pathogenesis of OA. PPARs are thus important proteins in OA regulation, which may have significant importance in OA therapeutics.

Neurodegeneration is the term describing the death of neurons both in the central nervous system and periphery. When affecting the central nervous system, it is responsible for diseases like Alzheimer\'s disease, Parkinson\'s disease, Huntington\'s disorders, amyotrophic lateral sclerosis, and other less frequent pathologies. There are several common pathophysiological elements that are shared in the neurodegenerative diseases. The common denominators are oxidative stress (OS) and inflammatory responses. Unluckily, these conditions are difficult to treat. Because of the burden caused by the progression of these diseases and the simultaneous lack of efficacious treatment, therapeutic approaches that could target the interception of development of the neurodegeneration are being widely investigated. This review aims to highlight the most recent proposed novelties, as most of the previous approaches have failed. Therefore, older approaches may currently be used by healthcare professionals and are not being presented.
This review was based on an electronic search of existing literature, using PubMed as primary source for important review articles, and important randomized clinical trials, published in the last 5 years. Reference lists from the most recent reviews, as well as additional sources of primary literature and references cited by relevant articles, were used.
Eighteen natural pharmaceutical substances and 24 extracted or recombinant products, and artificial agents that can be used against OS, inflammation, and neurodegeneration were identified. After presenting the most common neurodegenerative diseases and mentioning some of the basic mechanisms that lead to neuronal loss, this paper presents up to date information that could encourage the development of better therapeutic strategies.
This review shares the new potential pharmaceutical and not pharmaceutical options that have been recently introduced regarding OS and inflammatory responses in neurodegenerative diseases.

Chronic inflammatory conditions such as obesity, type-2 diabetes, and cardiovascular diseases are the leading causes of mortality worldwide. Hence, much research interest in bioactive peptides has been stimulated due to lack of potent pharmacological interventions. Although many such peptides have been identified from food proteins, insufficient information is available on their structure-function relationship. Presence of hydrophobic and positively charged amino acids is a common occurrence for the peptides with anti-inflammatory properties. However, inconsistent findings have also been reported. Most of the food-derived peptides exhibited their anti-inflammatory activities primarily by inhibiting signaling components of either NF-κB or MAPK pathway, which are the two major pathways involved in chronic inflammation following uncontrolled signal activation. This review highlighted the structural requirements of the peptides to exhibit anti-inflammatory activity based on the current knowledge about food-derived anti-inflammatory peptides and their underlying molecular mechanisms of action. PRACTICAL APPLICATIONS: While research in the food-derived bioactive peptide is gaining momentum, but the ability to translate these new findings into the commercial product such as nutraceuticals and functional foods, remains delayed. The most prominent reasons for this delay are the lack of detailed research on, (i) the structure-function relationship of the peptide and the underlying molecular mechanisms of these bioactive peptides, and (ii) the interaction of these peptides with different cellular elements in the disease pathophysiology. This review gives an insight into the structure-activity relationship of bioactive peptides involved in anti-inflammatory responses. The information provided here would be highly beneficial to describe the possible anti-inflammatory activity of any newly identified peptides from different food sources.

The pressing need to discover more effective drugs for various CNS disorders has resurrected the idea of investigating the effectiveness of traditional medicines in modern science. Tongluojiunao (TLJN) is an example of revived modern herbal preparation based on traditional Chinese medicine (TCM) with a long history of administration for various types of cerebrovascular injuries and neurodegenerative diseases. TLJN is prepared from the herbal roots of Panax notoginseng (Sanchi) and dried fruits of Gardenia jasminoides (Cape Jasmine), and so far, it has demonstrated promising results in patients with vascular dementia and cerebral ischemic stroke. TLJN has also demonstrated therapeutic ability regarding the slowly-progressed neurodegenerative diseases like Alzheimer\'s disease. So it tempted us to undertake a thorough review of various features of TLJN therapeutic effects on the mentioned CNS conditions, including the cellular and molecular targets, inflammatory responses, neurogenesis and angiogenesis mediators and cognitive function. For this purpose, multiple global and local databases, including China National Knowledge Infrastructure (CNKI) were checked out and the retrieved information was grouped according to their scope of studies. Among these, TLJN is reported to restore the deregulated cell-cell communication in the neurovascular unit, prevent the stress-related challenges imposed by ischemia/reperfusion insult, help with the cerebral tissue recovery after traumatic brain damage, avoid the epileptic seizure attack and limit the progression of Alzheimer\'s disease. We hope that the current review provides new insights into TLJN medication as a prospective neuroprotective medication for further more in-depth investigation in the future.