Particulate matter facilitates amphiregulin-dependent lung cancer proliferation through glutamine metabolism.

Although many cohort studies have reported that long-term exposure to particulate matter (PM) causes lung cancer, the molecular mechanisms underlying the PM-induced increases in lung cancer progression remain unclear. We applied the lung cancer cell line A549 (Parental; A549.Par) to PM for an extended period to establish a mimic PM-exposed lung cancer cell line, A549.PM. Our results indicate that A549.PM exhibits higher cell growth and proliferation abilities compared to A549.Par cells in vitro and in vivo. The RNA sequencing analysis found amphiregulin (AREG) plays a critical role in PM-induced cell proliferation. We observed that PM increases AREG-dependent lung cancer proliferation through glutamine metabolism. In addition, the EGFR/PI3K/AKT/mTOR signaling pathway is involved in PM-induced solute carrier family A1 member 5 (SLC1A5) expression and glutamine metabolism. Our findings offer important insights into how lung cancer proliferation develops upon exposure to PM.

Chlorogenic acid prevents ovariectomized-induced bone loss by facilitating osteoblast functions and suppressing osteoclast formation.

Osteoporosis is a usual bone disease in aging populations, principally in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are associated to a different of adverse effects. Du-Zhong is usually applied in Traditional Chinese Medicine to strengthen bone, regulate bone metabolism, and treat osteoporosis. Chlorogenic acid is a major polyphenol in Du-Zhong. In the current study, chlorogenic acid was found to enhance osteoblast proliferation and differentiation. Chlorogenic acid also inhibits the RANKL-induced osteoclastogenesis. Notably, ovariectomy significantly decreased bone volume and mechanical properties in the ovariectomized (OVX) rats. Administration of chlorogenic acid antagonized OVX-induced bone loss. Taken together, chlorogenic acid seems to be a hopeful molecule for the development of novel anti-osteoporosis treatment.

FGF23 facilitates IL-1ß synthesis in rheumatoid arthritis through activating PI3K, Akt, and NF-κB pathways.

Rheumatoid arthritis (RA) is a well-known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by osteocytes and osteoblasts, involves an essential effect in pathogenesis of RA. IL-1ß is a vital proinflammatory factor in the development of RA. However, the role of FGF23 on IL-1ß synthesis in RA has not been fully explored. Our analysis of database revealed higher levels of FGF23 and IL-1ß in RA samples compared with healthy controls. High-throughput screening demonstrated that IL-1ß is a potential candidate factor after FGF23 treatment in RA synovial fibroblasts (RASFs). FGF23 concentration dependently promotes IL-1ß synthesis in RASFs. FGF23 enhances IL-1ß expression by activating the PI3K, Akt, and NF-κB pathways. Our findings support the notion that FGF23 is a promising target in the remedy of RA.

CXCL13 promotes TNF-α synthesis in rheumatoid arthritis through activating ERK/p38 pathway and inhibiting miR-330-3p generation.

Rheumatoid arthritis (RA) is a well-known autoimmune disorder associated with joint pain, joint swelling, cartilage and bone degradation as well as deformity. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a crucial role in multiple cellular pathogenesis processes, including RA. TNF-α is a vital proinflammatory factor in the progression of RA. However, the role of CXCL13 in TNF-α production in RA has not been fully explored. Our analysis of both database and clinical samples revealed higher levels of CXCL13 and TNF-α in RA samples compared to healthy controls. CXCL13 concentration-dependently induces TNF-α synthesis in RA synovial fibroblasts. CXCL13 enhances TNF-α expression by interacting with the CXCR5 receptor, activating the ERK/p38 pathways, and inhibiting miR-330-3p generation. Importantly, treatment with CXCL13 shRNA counteracted the upregulation of TNF-α production induced by collagen-induced arthritis. Our findings support the notion that CXCL13 is a promising target in the treatment of RA.

High-mobility group box-1 impedes skeletal muscle regeneration via downregulation of Pax-7 synthesis by increasing miR-342-5p expression.

High mobility group box-1 (HMGB1) is a driver of inflammation in various muscular diseases. In a previous study, we determined that HMGB1 induced the atrophy of skeletal muscle by impairing myogenesis. Skeletal muscle regeneration after injury is dependent on pair box 7 (Pax-7)-mediated myogenic differentiation. In the current study, we determined that the HMGB1-induced downregulation of Pax-7 expression in myoblasts inhibited the regeneration of skeletal muscle. We also determined that HMGB1 inhibits Pax-7 and muscle differentiation by increasing miR-342-5p synthesis via receptors for advanced glycation end-products (RAGE), toll-like receptor (TLR) 2, TLR4, and c-Src signaling pathways. In a mouse model involving glycerol-induced muscle injury, the therapeutic inhibition of HMGB1 was shown to rescue Pax-7 expression and muscle regeneration. The HMGB1/Pax-7 axis is a promising therapeutic target to promote muscular regeneration.

Ugonin L inhibits osteoclast formation and promotes osteoclast apoptosis by inhibiting the MAPK and NF-κB pathways.

Bone loss is a major issue for patients with osteoporosis, arthritis, periodontitis, and bone metastasis; however, anti-resorption drugs used to treat bone loss have been linked to a variety of adverse effects. Helminthostachys zeylanica (L.) Hook, belonging to the family Ophioglossaceae, is commonly used in traditional Chinese medicine to treat inflammation and liver problems. In the current study, ugonin L extracted from H. zeylanica was shown to reduce the receptor activator of nuclear factor kappa beta ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells in a concentration-dependent manner. Ugonin L treatment also inhibited the mRNA expression of osteoclast markers. Ugonin L was also shown to promote cell apoptosis in mature osteoclasts and suppress RANKL-induced ERK, p38, JNK, and NF-κB activation. Taken together, ugonin L appears to be a promising candidate for the development of novel anti-resorption therapies.

HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism.

Skeletal muscle atrophy occurs due to muscle wasting or reductions in protein associated with aging, injury, and inflammatory processes. High-mobility group box-1 (HMGB1) protein is passively released from necrotic cells and actively secreted by inflammatory cells, and is implicated in the pathogenesis of various inflammatory and immune diseases. HMGB1 is upregulated in muscle inflammation, and circulating levels of the proinflammatory cytokine interleukin-18 (IL-18) are upregulated in patients with sarcopenia, a muscle-wasting disease. We examined whether an association exists between HMGB1 and IL-18 signaling in skeletal muscle atrophy. HMGB1-induced increases of IL-18 levels enhanced the expression of muscle atrophy markers and inhibited myogenic marker expression in C2C12 and G7 myoblast cell lines. HMGB1-induced increases of IL-18 production in C2C12 cells involved the RAGE/p85/Akt/mTOR/c-Jun signaling pathway. HMGB1 short hairpin RNA (shRNA) treatment rescued the expression of muscle-specific differentiation markers in murine C2C12 myotubes and in mice with glycerol-induced muscle atrophy. HMGB1 and IL-18 signaling was suppressed in the mice after HMGB1 shRNA treatment. These findings suggest that the HMGB1/IL-18 axis is worth targeting for the treatment of skeletal muscle atrophy.

Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.