Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Sinomenine inhibits macrophage M1 polarization by downregulating α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1.

BACKGROUND: Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis. In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. PURPOSE: To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. METHODS: The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro, α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. RESULTS: SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. CONCLUSIONS: SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro. The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.

Vitamin D: preventive and therapeutic potential in Parkinson's disease.

Vitamin D is one of the important nuclear steroid transcription regulators that controls transcriptions of a large number of genes. Vitamin D supplement is commonly recommended for the elderly to prevent bone diseases. Amounting new evidence has indicated that vitamin D plays a crucial role in brain development, brain function regulation and neuroprotection. Parkinson's disease (PD) is a degenerative disorder commonly seen in the elderly, characterized by movement disorders including tremor, akinesia, and loss of postural reflexes. The motor symptoms largely result from the continued death of dopaminergic neurons in the substantia nigra, despite use of current therapeutic interventions. The cause and mechanism of neuron death is currently unknown. Vitamin D deficiency is common in patients with PD suggesting its preventive and therapeutic potential. Vitamin D may exert protective and neurotropic effects directly at cellular level, e.g. protection of dopamine system, and/or by regulating gene expression. This review summarizes the epidemiological, genetic and translational evidence implicating vitamin D as a candidate for prevention and treatment for PD.

[Effect of total saponins from Panax notoginseng on expession of melatonin receptor mRNA in gastric mucosa of stress rats].

OBJECTIVE: To observe the effect of total saponins from Panax notoginseng (PNS) on melatonin receptor (MR) expression and its content in gastric mucosa of stress rats. METHODS: Water-immersion restraint stress (WRS) was used to induce stress rat models. RevertAid First Strand cDNA Synthesis Kit was used for the reverse transcription of the total RNA from gastric mucosa of stress rats. The PCR product was analyzed by agarose gel electrophoresis firstly and then by KODAK 1 D Image system. The expression level of melatonin 1 (MT1) receptor mRNA was calculated with the optimal density of ratio of MT, receptor and GAPDH. RESULTS: Six hours after WRS, there were 360 bp positive bands in RT-PCR product of MT1. The relative content of MR was lower in the model group than that in the normal group. MR content in PNS group and ranitidine group were both higher than that in the normal group and the model group (P < 0.05 or P < 0.01). CONCLUSION: There is mRNA expression of MT1 receptor in gastric mucosa of stress rats indeed. PNS has protective effect on gastric mucosa of stress rats by up-regulating MR expression, and its protective mechanism may be related to promoting melatonin secretion or increasing the binding capacity of melatonin to its receptor.

[Effect of Kuijieling decoction on proteins expression of IKK-alpha in colonic mucosa of ulcerative colitis model rats].

OBJECTIVE: To explore the changes of protein expression of IKK-alpha as well as the effects of Kuijieling Decoction (KD) on colonic mucosa of ulcerative colitis (UC) model rats. METHODS: UC model rats were induced by TNBS. The rats were randomly divided into six groups: normal control (NC) group, model control (MC) group, Kuijieling low dose (KLD), middle dose (KMD) group, high dose (KHD) group and SASP group. After 10-days' treatment the rats were killed to get their colonic tissues. The positive rate of IKK-alpha expression was detected by immunohistochemical (IHC). RESULTS: The positive rate of IKK-alpha in MC group was significantly higher than that in NC group (P < 0.01). The positive rate of IKK-alpha in KMD group was significantly lower than that in MC group (P < 0.05). The positive rate of IKK-alpha in KHD and SASP group were significantly lower than that in MC group (P < 0.01). CONCLUSION: IKK-alpha may be involved in the pathogenesis of UC, and KD can inhibit positive rate of IKK-alpha in colonic mucosa of UC model rats induced by TNBS. The inhibitory effects of KD on UC may be associated with this.