Nonalcoholic fatty liver disease (NAFLD) has become the world's largest chronic liver disease, while there is still no specific drug to treat NAFLD. Traditional Chinese Medicine (TCM) have been widely used in hepatic diseases for centuries in Asia, and TCM’s holistic concept and differentiation treatment of NAFLD show their advantages in the treatment of this complex metabolic disease. However, the multi-compounds and multi-targets are big obstacle for the study of TCM. Here, we summarize the pharmacological actions of active ingredients from frequently used single herbs in TCM compounds. The combined mechanism of herbs in TCM compounds are further discussed to explore their comprehensive effects on NAFLD. This article aims to summarize multiple functions and find the common ground for TCM treatment on NAFLD, thus providing enrichment to the scientific connotation of TCM theories and promotes the exploration of TCM therapies on NAFLD.

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Traditional Chinese Medicine in nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives.

Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of the spinal cord, which significantly impacts the quality of life in affected patients. The phosphoinositide 3kinase/serine‐threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for the inhibition of secondary TSCI. This review summarizes updates concerning the role of the PI3K/AKT pathway in TSCI.

The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

mTOR pathway: A potential therapeutic target for spinal cord injury.

mTOR pathway: A potential therapeutic target for spinal cord injury

Spinal cord injury (SCI) is a catastrophic condition with high morbidity and mortality that still lacks effective therapeutic strategies. It is well known that the most important stage in SCI pathogenesis is secondary injury, and among the involved mechanisms, the inflammatory cascade is the main contributor and directly influences neurological function recovery. In recent years, increasing evidence has shown that mesenchymal stem cells (MSCs) transplantation is a promising immunomodulatory strategy. Transplanted MSCs can regulate macrophage-, astrocyte-, and T lymphocyte-mediated neuroinflammation and help create a microenvironment that facilitates tissue repair and regeneration. This review focuses on the effects of different types of immune cells and MSCs, specifically the immunoregulatory capacity of MSCs in SCI and repair. We will also discuss how to exploit MSCs transplantation to regulate immune cells and develop novel therapeutic strategies for SCI. 

https://www.dovepress.com/getfile.php?fileID=77850

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

Spinal cord injury (SCI) is a salient traumatic disease that often leads to permanent disability, and motor and sensory impairments. Human umbilical cord mesenchymal stem cells (HucMSCs) have a wide application prospect in the treatment of SCI. This study explored the repair effect of HucMSCs-derived extracellular vesicles (HucMSCs-EVs) on SCI. HucMSCs and HucMSCs-EVs were cultured and identified. The rat model of SCI was established, and SCI rats were treated with HucMSCs-EVs. The motor function of SCI rats and morphology of spinal cord tissues were evaluated. Levels of NeuN, GFAP, and NF200 in spinal cord tissues were detected and cell apoptosis was measured. SCI rats were treated with EVs extracted from miR-29b-3p inhibitor-transfected HucMSCs. The downstream gene and pathway of miR-29b-3p were examined. HucMSCs-EVs-treated rats showed obvious motor function recovery and reduced necrosis, nuclear pyknosis, and cavity. HucMSCs-EVs alleviated spinal cord neuronal injury. miR-29b-3p was poorly expressed in SCI tissues, but highly expressed in EVs and SCI rats treated with EVs. miR-29b-3p targeted PTEN. Inhibition of miR-29b-3p or overexpression of PTEN reversed the repair effect of EVs on SCI. EVs activated the AKT/mTOR pathway via the miR-29b-3p/PTEN. In conclusion, HucMSCs-EVs reduced pathological changes, improved motor function, and promoted nerve function repair in SCI rats via the miR-29b-3p/PTEN/Akt/mTOR axis.

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Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis.

SIRT1 provides new pharmacological targets for polydatin through its role as a metabolic sensor.

To evaluate the mid-long-term outcomes of surgical management of mono-segmental lumbar and lumbosacral spinal tuberculosis (TB) in adults by one-stage posterior debridement, single-segment fixation, and titanium mesh cage interbody fusion. A total of 62 patients with mono-segmental lumbar or lumbosacral spinal tuberculosis were enrolled. One-stage posterior debridement, single-segment fixation, and titanium mesh cage interbody fusion was performed. Clinical and radiographic outcomes were compared and analyzed. All patients were followed-up for an average of 75.0 ± 11.5 months and completely cured at the final follow-up. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) returned to normal within three months postoperatively. Postoperative Japanese Orthopedic Association (JOA) score, visual analog scale (VAS) and Oswestry Disability index (ODI) were significantly improved compared with preoperative values. Bony fusion occurred after an average of 9.8 ± 2.6 months. The lordosis angle and lumbosacral angle were increased from preoperative 20.4 ± 2.9° and 14.7 ± 3.4° to postoperative 32.8 ± 3.6° and 22.4 ± 5.5°, with angle loss of 1.0 ± 0.7° and 0.8 ± 0.7° at the final follow-up, respectively. No significant differences between preoperative and postoperative adjacent segment disc height (DH) were found. One-stage posterior debridement, single-segment fixation, and titanium mesh cage interbody fusion represent effective and feasible treatment option for mono-segmental lumbar and lumbosacral spinal tuberculosis in adults. This approach may preserve lumbar normal motor units and decrease adjacent segment degeneration (ASD) with the advantages of minimal invasiveness and rapid postoperative rehabilitation.

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One-stage posterior debridement and single-segment interbody fusion for treating mono-segmental lumbar and lumbosacral spinal tuberculosis in adults following minimum 5-year follow-up.

To explore the therapeutic effect of early surgical intervention for active thoracic spinal tuberculosis (TB) patients with paraparesis and paraplegia. Data on 118 active thoracic spinal TB patients with paraparesis and paraplegia who had undergone surgery at an early stage (within three weeks of paraparesis and paraplegia) from January 2008 to December 2014 were retrospectively analyzed. The operation duration, blood loss, perioperative complication rate, VAS score, ASIA grade and NASCIS score of neurological status rating, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), kyphotic Cobb’s angle, and duration of bone graft fusion were analyzed to evaluate the therapeutic effects of surgery. The mean operating time was 194.2 minutes, and the mean blood loss was 871.2 ml. The perioperative complication rate was 5.9 %. The mean preoperative VAS score was 5.3, which significantly decreased to 3.2 after the operation and continued decreasing to 1.1 at follow up (P 0.05), then gradually decreased to 11.5 ± 1.8 mm/h and 2.6 ± 0.82 mg/L, respectively, at final follow up (P 0.05). The mean duration of bone graft fusion was 8.6 ± 1.3 months. Early surgical intervention may be beneficial for active thoracic spinal TB patients with paraparesis and paraplegia, with surgical intervention being more beneficial for recovery from paraparesis than paraplegia.

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Early surgical intervention for active thoracic spinal tuberculosis patients with paraparesis and paraplegia

Following recent advances in osteoimmunology, there is growing recognition of the vital role of immune cells in the osteogenesis process. The 3D-printed scaffold, as a substitute for injured and/or diseased bone tissues, has demonstrated satisfactory pro-osteogenetic performance. However, whether immune cells prompt the above pro-osteogenetic performance has not been elucidated in detail. In the present study, highly controllable Ti-6Al-4V scaffolds with different pore geometries were fabricated using a selective laser-melting technique, to reveal their osteoimmunological functions with macrophages. The results showed that macrophages displayed characteristics of M2 phenotype in response to scaffolds. As a result, an anti-inflammatory microenvironment was generated. When the pore geometry was considered, such observations were more apparent with the hexagonal pore scaffold than with the triangular one. In addition, inhibition of the toll-like receptor signaling pathway in macrophages has been proposed to cause the above phenomenon. Upon applying conditioned media derived from macrophages on pre-osteoblasts, the hexagonal pore scaffold group was found to significantly enhance osteoblastic differentiation, via macrophage-to-implant interactions. However, the effect of triangular pore scaffold was not statistically significant compared to that of hexagonal pore scaffolds or nonporous samples. In an attempt to quantify scaffold pore geometries, it was suggested that pores with higher circularity values tended to induce M2 polarization of macrophages, promote an anti-inflammatory milieu, and therefore, achieve better osteogenetic performance via immunomodulation.

Macrophage responses to selective laser-melted Ti-6Al-4V scaffolds of different pore geometries and the corresponding osteoimmunomodulatory effects toward osteogenesis.

Xu Zhenchao

Papers

Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis.

SIRT1 provides new pharmacological targets for polydatin through its role as a metabolic sensor.

One-stage posterior debridement and single-segment interbody fusion for treating mono-segmental lumbar and lumbosacral spinal tuberculosis in adults following minimum 5-year follow-up.

Early surgical intervention for active thoracic spinal tuberculosis patients with paraparesis and paraplegia

Macrophage responses to selective laser-melted Ti-6Al-4V scaffolds of different pore geometries and the corresponding osteoimmunomodulatory effects toward osteogenesis.