Therapeutic potential of Scutellaria baicalensis Georgi in lung cancer therapy.

Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion and metastasis, extracellular matrix remodeling, immune suppression, as well as chemotherapy resistance. Classically activated type I macrophages (M1) exhibited marked tumor killing and phagocytosis. Therefore, using macrophages for adoptive cell therapy has attracted attention and become one of the most effective strategies for cancer treatment. Through cytokines and/or chemokines, macrophage can inhibit myeloid cells recruitment, and activate anti-tumor and immune killing functions. Applying macrophages for anti-tumor delivery is one of the most promising approaches for cancer therapy. This review article introduces the role of macrophages in tumor development and drug resistance, and the possible clinical application of targeting macrophages for overcoming drug resistance and enhancing cancer therapeutics, as well as its challenges. 

The promising role of tumor-associated macrophages in the treatment of cancer.

The incidence and disability rate of spinal cord injury (SCI) worldwide are high, imposing a heavy burden on patients. Considerable research efforts have been directed toward identifying new strategies to effectively treat SCI. Governor Vessel electro‐acupuncture (GV‐EA), used in traditional Chinese medicine, combines acupuncture with modern electrical stimulation. It has been shown to improve the microenvironment of injured spinal cord (SC) by increasing levels of endogenous neurotrophic factors and reducing inflammation, thereby protecting injured neurons and promoting myelination. In addition, axons extending from transplanted stem cell‐derived neurons can potentially bridge the two severed ends of tissues in a transected SC to rebuild neuronal circuits and restore motor and sensory functions. However, every single treatment approach to severe SCI has proven unsatisfactory. Combining different treatments—for example, electro‐acupuncture (EA) with adult stem cell transplantation—appears to be a more promising strategy. In this review, we have summarized the recent progress over the past two decades by our team especially in the use of GV‐EA for the repair of SCI. By this strategy, we have shown that EA can stimulate the nerve endings of the meningeal branch. This would elicit the dorsal root ganglion neurons to secrete excess amounts of calcitonin gene‐related peptide centrally in the SC. The neuropeptide then activates the local cells to secrete neurotrophin‐3 (NT‐3), which mediates the survival and differentiation of donor stem cells overexpressing the NT‐3 receptor, at the injury/graft site of the SC. Increased local production of NT‐3 facilitates reconstruction of host neural tissue such as nerve fiber regeneration and myelination. All this events in sequence would ultimately strengthen the cortical motor‐evoked potentials and restore the motor function of paralyzed limbs. The information presented herein provides a basis for future studies on the clinical application of GV‐EA and adult stem cell transplantation for the treatment of SCI.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cns.13813

Electro‐acupuncture and its combination with adult stem cell transplantation for spinal cord injury treatment: A summary of current laboratory findings and a review of literature

Objective To explore and analyze the effects of acupuncture and medical treatment at different times on the gastrointestinal reaction and leukocyte count of patients with lung cancer undergoing chemotherapy. Methods Select 224 lung cancer chemotherapy patients admitted to our hospital and randomly divide them into three groups: control group (n = 76), study 1 group (n = 78), and study 2 group (n = 70). The control group was treated with tropisetron hydrochloride for 30 minutes before chemotherapy. Study 1 group was given tropisetron hydrochloride and acupuncture combination therapy 30 minutes before chemotherapy. Study 2 group was given tropisetron hydrochloride treatment 30 min before chemotherapy and acupuncture treatment 30 min after chemotherapy. Collect patients' general information and compare the three groups of white blood cell count, G-CSF, GM-CSF levels, quality of life and KPS score, platelets, neutrophils, hemoglobin levels, TCM symptom scores, and the degree of digestive tract reaction. Results The data of the control group and study groups 1 and 2 are comparable in gender, age, pathological type, etc. (P > 0.05). Before treatment, the white blood cell counts of the three groups were not significantly different (P > 0.05), significantly reduced after treatment, but the difference between the groups was not statistically significant (P > 0.05). The levels of G-CSF and GM-CSF in the three groups were not substantially different before treatment (P > 0.05). The levels of G-CSF and GM-CSF were considerably lowered in all three groups, although the drop in the study group was more significant (P > 0.05) when compared to that in the control group. Before treatment, the quality of life and KPS score of the three groups were not statistically different (P > 0.05). The three groups' quality of life and KPS scores fell after treatment, with the study 1 group experiencing the greatest reduction, followed by the study 2 group and the control group. The levels of platelets, neutrophils, and hemoglobin in all three groups declined dramatically, with the most noticeable reduction in the control group, followed by study 2 and study 1. The difference between the three groups was statistically significant (P < 0.05). The TCM symptom scores of the three groups showed an upward trend, but compared with those of the study 1 group and study 2 group, the TCM symptom scores of the control group increased significantly and the difference between the three groups was statistically significant (P < 0.05). The effective rates of the control group, study group 1, and study group 2 were 42.11%, 82.05%, and 62.86%, respectively; compared with that of the control group, the treatment efficiency of study groups 1 and 2 was higher and the difference between the three groups was statistically significant (P < 0.05). Conclusion Tropisetron hydrochloride is an effective treatment for patients with lung cancer before chemotherapy, which can effectively improve the side effects of nausea and vomiting caused by chemotherapy, reduce the white blood cell count, and improve the quality of life of patients; it plays an important role in the improvement of prognosis.

/pdf/to-explore-the-effects-of-acupuncture-and-medical-treatment-1uhel7a6.pdf

To Explore the Effects of Acupuncture and Medical Treatment at Different Times on the Gastrointestinal Reaction and White Blood Cell Count of Patients with Lung Cancer Chemotherapy

Skin wounds significantly impact the global health care system and represent a significant burden on the economy and society due to their complicated dynamic healing processes, wherein a series of immune events are required to coordinate normal and sequential healing phases, involving multiple immunoregulatory cells such as neutrophils, macrophages, keratinocytes, and fibroblasts, since dysfunction of these cells may impede skin wound healing presenting persisting inflammation, impaired vascularization, and excessive collagen deposition. Therefore, cellular target-based immunomodulation is promising to promote wound healing as cells are the smallest unit of life in immune response. Recently, immunomodulatory hydrogels have become an attractive avenue to promote skin wound healing. However, a detailed and comprehensive review of cellular targets and related hydrogel design strategies remains lacking. In this review, the roles of the main immunoregulatory cells participating in skin wound healing are first discussed, and then we highlight the cellular targets and state-of-the-art design strategies for immunomodulatory hydrogels based on immunoregulatory cells that cover defect, infected, diabetic, burn and tumor wounds and related scar healing. Finally, we discuss the barriers that need to be addressed and future prospects to boost the development and prosperity of immunomodulatory hydrogels.

Immunomodulatory hydrogels for skin wound healing: cellular targets and design strategy.

Acupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic–pituitary–adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.

/pdf/the-role-of-macrophage-polarization-and-associated-4xkk2n3uzc.pdf

The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives.

Objective As a first-line treatment for non-small cell lung cancer (NSCLC), the efficacy of chemotherapy is still unsatisfactory. Moxibustion has been shown to improve the side effects of radiotherapy and chemotherapy and regulate immune function. This study aimed to explore the antitumor effects and potential mechanisms of combinatorial cisplatin and moxibustion treatment for NSCLC by targeting the tumor microenvironment. Methods Lewis lung cancer (LLC)-bearing mice were induced and treated with cisplatin or/and moxibustion at ST36 (Zusanli), and the growth, weight, and area of the tumor were evaluated. The numbers of various T cell subsets and myeloid cells in the tumor were assessed by flow cytometry, and the gene expression of related markers and cytokines was detected with real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the tumor vascular structure was investigated using CD31 and α-smooth muscle actin (α-SMA) immunofluorescence staining. The expression of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) was detected by immunohistochemical staining. Results Both cisplatin and moxibustion inhibited LLC tumor growth and reduced both the tumor area and weight, with the combinatorial therapy showing superior outcomes. Moxibustion upregulated the infiltration of CD4+ T cells and Th1 cells in the tumor, and the combinatorial therapy increased the proportion of CD8+ cytotoxic T cells (CTLs), CD4+T cells, Th1, Th9 cells, and M1 macrophages, as well as the expression of Cd69, Ifng, and Cd86 mRNA. The combinatorial therapy improved vascular normalization by increasing both the microvessel density (MVD) and pericyte coverage (α-SMA area density) and inhibiting the expression of the VEGF. Conclusions Combinatorial cisplatin and moxibustion treatment inhibited the LLC tumor growth by mechanisms related to the improvement of the tumor immune microenvironment and vascular normalization, providing an effective combinatorial therapy beneficial for patients with NSCLC.

/pdf/the-combinatorial-effect-of-cisplatin-and-moxibustion-on-o9v4mbzd7d.pdf

The Combinatorial Effect of Cisplatin and Moxibustion on Tumor Growth Inhibition with Special Reference to Modulation of the Immune Microenvironment in Lewis Lung Cancer Mice.

Platinum-based chemotherapy is an effective treatment used in multiple tumor treatments, but produces severe side effects including neurotoxicity, anemia, and immunosuppression, which limits its anti-tumor efficacy and increases the risk of infections. Electroacupuncture (EA) is often used to ameliorate these side effects, but its mechanism is unknown. Here, we report that EA on ST36 and SP6 prevents cisplatin-induced neurotoxicity and immunosuppression. EA induces neuroprotection, prevents pain-related neurotoxicity, preserves bone marrow (BM) hematopoiesis, and peripheral levels of leukocytes. EA activates sympathetic BM terminals to release pituitary adenylate cyclase activating polypeptide (PACAP). PACAP-receptor PAC1-antagonists abrogate the effects of EA, whereas PAC1-agonists mimic EA, prevent neurotoxicity, immunosuppression, and preserve BM hematopoiesis during cisplatin chemotherapy. Our results indicate that PAC1-agonists may provide therapeutic advantages during chemotherapy to treat patients with advanced neurotoxicity or neuropathies limiting EA efficacy.

PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.

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The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives.

The Combinatorial Effect of Cisplatin and Moxibustion on Tumor Growth Inhibition with Special Reference to Modulation of the Immune Microenvironment in Lewis Lung Cancer Mice.

PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.