Objective To investigate TXNIP and KLF9 expressions in the tissues of colorectal cancer(CRC)and their impact on clini-cal characteristics and prognosis.Methods This study included 90 CRC patients who were admitted to our hospital between January 2017 and December 2020.The cancer tissue and paired adjacent tissues removed surgically were collected.We performed detection and analysis of TXNIP and KLF9 protein expression levels in cancer and adjacent tissues and their correlation with clinical characteristics and overall survival rate of patients.Results GEPIA database analysis showed that TXNIP and KLF9 mRNA expression levels in READ tissues were significantly lower than those in normal tissues(P＜0.05).The positive expression rates of TXNIP and KLF9 in CRC tissues were 32.22％and 37.78％,respectively,which were lower than those in adjacent tissues(73.33％and 76.67％,respectively;P＜0.05).TXNIP and KLF9 expressions were positively correlated(r=0.519,P＜0.05),and GEPIA database retrieval showed a positive correlation between TXNIP and KLF9 expressions(P＜0.05).TXNIP and KLF9 expressions in patients with clinical stage Ⅲ and lymph node metas-tasis were lower than those in patients with stage Ⅰ/Ⅱ and non-lymph node metastasis(P＜0.05).The overall survival rate of patients with TXNIP and KLF9 expressions was higher than that of patients without TXNIP and KLF9 expressions.Negative expression of TXNIP and KLF9 in TNM stage Ⅲ was a prognostic risk factor(P＜0.05).Conclusion TXNIP and KLF9 expression levels are low in CRC tissues and associated with TNM stage,lymph node metastasis,and poor survival.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the targeting of transforming growth factor β1(TGF-β1)expression by Ran-binding protein 9(RANBP9)and its effect on colorectal cancer Colo320 cell apoptosis.Methods Gene expression levels of RANBP9 were analyzed in 625 colon cancer tissues and 20 normal colon tissues in The Cancer Genome Atlas database.The relationship between RANBP9 expression and survival time of patients with colon cancer was analyzed using KMPLOT.The expression of TGF-β1 in normal colon tissues and colon cancer tissues was analyzed using the human protein immunohistochemistry database and the relationship between TGF-β1 expression and the survival of patients with colon cancer was analyzed using the UALCAN database.The relationship between RANBP9 and TGF-β1 was analyzed by dual luciferase experiments.Colo320 cells were transfected with pcDNA3.1-GFP-RANBP9 and control pcDNA3.1-GFP-RANBP9-NC plasmids,respectively,and normal control cells were established without transfection.The cells were cultured and the growth viability of each group of cells was detected by the iazolyl blue tetrazolium bromide method,apoptosis was detected by flow cytometry,the mitochondrial membrane potential was detected by JC-1 staining,and RANBP9 and TGF-β1 protein expression were detected by Western blot.Results RANBP9 expression was significantly reduced in colon cancer tissues.Compared with patients with low RANBP9 expression,patients with high RANBP9 expression had a higher survival curve and significantly higher expression of TGF-β1 in colon cancer tissue.Compared with patients with high TGF-β1 expression,patients with low TGF-β1 expression had a significantly higher survival curve(P＜0.05).RANBP9 targeted the expression of TGF-β1 in colon cancer.Compared with the normal group,cell growth,mitochondrial membrane potential,and TGF-β1 expression were all significantly down-regulated and the apoptosis rate and RANBP9 expression were significantly increased in the experiment group(P＜0.05).Conclusions RANBP9 can target the expression of TGF-β1,promote the growth of Colo320 colon cancer cells,decrease the mitochondrial membrane potential,and induce apoptosis.