Fig 2: Expression levels of TRPV1 and associated molecules in the PFC. The expression pattern of TRPV1 protein was detected in the following groups: WT-HFD; WT-HFD-ACE; WT-HFD-SHAM; and KO-HFD. The results demonstrated significant decreases in (A) TRPV1 expression in WT-HFD, WT-HFD-SHAM and KO-HFD groups when compared with the WT-HFD-ACE group, which demonstrated a significant increase following ACE treatment. *P<0.05. The results also demonstrated significant decreases in (B) p-PI3K (C) p-Akt (D) p-mTOR (E) p-PKCε (F) p-PKAIIα (G) p-ERK (H) p-p38 (I) p-JNK (J) p-NF-κB and (K) p-CREB expression levels in the WT-HFD and WT-HFD-SHAM groups compared with the other groups. *P<0.05. The expression levels of these proteins were statistically increased in the WT-HFD-ACE and KO-HFD groups. *P<0.05. TRPV1, transient receptor vanilloid member 1; WT, wild-type; ND, normal diet; HFD, high-fat diet; ACE, acupoint catgut embedding; KO, knockout; PFC, prefrontal cortex; p, phosphorylated; PKCε. protein kinase C epsilon type; PKAIIα, protein kinase AII α; ERK, extracellular signal-regulated kinase; p38, p38 mitogen-activated protein kinase; JNK, c-Jun N-terminal kinase; CREB, cyclic AMP-response element binding protein.

Fig 3: Expression levels of TRPV1 and associated molecules in the hypothalamus. The expression pattern of TRPV1 protein was detected in the following groups: WT-HFD; WT-HFD-ACE; WT-HFD-SHAM; and KO-HFD. The results revealed significant increases in (A) TRPV1, (B) p-PI3K, (C) p-Akt, (D) p-mTOR, (E) p-PKCε, (F) p-PKAIIα, (G) p-ERK, (H) p-p38, (I) p-JNK, (J) p-NF-κB and (K) p-CREB expression levels in the WT-HFD and WT-HFD-SHAM groups compared with the other groups (*P<0.05). These increases were statistically decreased in the WT-HFD-ACE group that received ACE treatment and in the KO-HFD group that lacked the TRPV1 receptor. *P<0.05. TRPV1, transient receptor vanilloid member 1; WT, wild-type; ND, normal diet; HFD, high-fat diet; ACE, acupoint catgut embedding; KO, knockout; p, phosphorylated; PKCε, protein kinase C epsilon type; PKAIIα, protein kinase AII α; ERK, extracellular signal-regulated kinase; p38, p38 mitogen-activated protein kinase; JNK, c-Jun N-terminal kinase; CREB, cyclic AMP-response element binding protein.

Fig 4: DLC1 inhibition is critical for mir-141-3p to activate the p38MAPK pathway(A) pRNAT-U6.1/Neo expression vector. (B) Two shRNA constructs and the corresponding primers. (C) Two shRNA constructs stably silence DLC1 in osteoblasts. (D) DLC1 KD activated RhoA and CDC42 and affected p38MAPK phosphorylation. (E) CDC42 inhibition significantly affected p38MAPK phosphorylation.

Fig 5: miR-141-3p-promoted osteoblast activity is p38MAPK dependent(A) Expression of osteoblast activity-related marker genes in osteoblasts. (B) DLC1-p38MAPK signalling in prostate cancer bone metastasis.