Awake cardiac surgery using the novel pectoralis-intercostal-rectus sheath (PIRS) plane block and subxiphoid approach.

BACKGROUND: Postoperative pain after cardiac surgery is a very important issue and affects recovery, risk of postoperative complications and quality of life. The pain management has been traditionally based on intravenous opioids with growing evidence suggesting the use of opioid-free and opioid-sparing techniques to reduce its adverse effects. CASE PRESENTATION: We report the case of a 75-year-old frail patient underwent awake mediastinal revision with subxiphoid access due to deep sternal wound infection using a pectoralis-intercostal rectus sheath (PIRS) plane block. During the procedure the patient never reported pain receiving acetaminophen 1 g every 8 h for postoperative pain management without others pain relievers. CONCLUSION: Ultrasound guided PIRS block could be an effective and safe analgesic technique to manage sternal and subxiphoid drainage pain in patients undergoing cardiac surgery via subxiphoid approach.

Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1.

Protein phosphatase 2A (PP2A) critically regulates cell signaling and is a human tumor suppressor. PP2A complexes are modulated by proteins such as cancerous inhibitor of protein phosphatase 2A (CIP2A), protein phosphatase methylesterase 1 (PME-1), and SET nuclear proto-oncogene (SET) that often are deregulated in cancers. However, how they impact cellular phosphorylation and how redundant they are in cellular regulation is poorly understood. Here, we conducted a systematic phosphoproteomics screen for phosphotargets modulated by siRNA-mediated depletion of CIP2A, PME-1, and SET (to reactivate PP2A) or the scaffolding A-subunit of PP2A (PPP2R1A) (to inhibit PP2A) in HeLa cells. We identified PP2A-modulated targets in diverse cellular pathways, including kinase signaling, cytoskeleton, RNA splicing, DNA repair, and nuclear lamina. The results indicate nonredundancy among CIP2A, PME-1, and SET in phosphotarget regulation. Notably, PP2A inhibition or reactivation affected largely distinct phosphopeptides, introducing a concept of nonoverlapping phosphatase inhibition- and activation-responsive sites (PIRS and PARS, respectively). This phenomenon is explained by the PPP2R1A inhibition impacting primarily dephosphorylated threonines, whereas PP2A reactivation results in dephosphorylation of clustered and acidophilic sites. Using comprehensive drug-sensitivity screening in PP2A-modulated cells to evaluate the functional impact of PP2A across diverse cellular pathways targeted by these drugs, we found that consistent with global phosphoproteome effects, PP2A modulations broadly affect responses to more than 200 drugs inhibiting a broad spectrum of cancer-relevant targets. These findings advance our understanding of the phosphoproteins, pharmacological responses, and cellular processes regulated by PP2A modulation and may enable the development of combination therapies.

Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome.

BACKGROUND: Hesperidin has been reported to have biological activities such as antihypertensive, hypoglycemic, and antioxidant effects. This study investigated whether hesperidin could improve signs of the metabolic syndrome and cardiac function in a high-fat diet (HFD) induced metabolic syndrome (MS) in rats. METHODS: Male Sprague-Dawley rats were fed HFD and 15% fructose for 16 weeks and treated with hesperidin (15 or 30 mg/kg, based on signs of MS from a preliminary study) or metformin, a positive control agent, (100 mg/kg) for the final four weeks. Cardiac function, blood pressure, fasting blood glucose, oral glucose tolerance, serum insulin, and lipid profiles were measured. Histomorphometrics of left ventricles, epidydimal fat pads and liver were evaluated. Expressions of phosphorylate insulin receptor substrate1(p-IRS1), p-Akt and GLUT4 in cardiac tissue were determined. RESULTS: Hesperidin and metformin attenuated MS in HFD rats (p < 0.05). The accumulation of visceral fat pads and fatty liver associated with increases in liver lipid contents and liver enzymes were found in MS rats that were alleviated in hesperidin or metformin-treated groups (p < 0.05). Hesperidin and metformin improved cardiac dysfunction and hypertrophy observed in MS rats (p < 0.05). Restoration of the insulin signaling pathway, IRS/Akt/GLUT4 protein expression, was demonstrated in hesperidin and metformin-treated groups (p < 0.05). Hesperidin (30 mg/kg) was more effective than the lower dose. CONCLUSION: Hesperidin was effective in reducing signs of MS and alterations of LV hypertrophy and function. These beneficial effects on the heart were associated with the restoration of the cardiac insulin signaling pathway in MS rats.

Modified percutaneous internal ring suturing with peritoneal injury in children: matched comparison to open hernia repair.

BACKGROUND: The aim of this study was to elucidate the outcomes of percutaneous internal ring suture (PIRS) technique for inguinal hernia repair augmented with thermal peritoneal injury compared to open inguinal hernia repair (OHR) in a large population of contemporary pediatric patients. Thermal injury with PIRS has been shown to reduce recurrence in animal models and is increasingly being incorporated into clinical practice. METHODS: Retrospective review of all PIRS procedures and OHR between Jan-2017 to Sept-2018 was performed. Data regarding patient characteristics, characteristics of the hernia, operative details, postoperative complications, and recurrence were collected. Non-parametric tests were used and p < 0.05 was regarded as statistically significant. 1:1 Propensity score matching was performed using "nearest-score" technique. Matching was done based on age, sex, follow-up time, side of hernia, repair of contralateral hernia, and number of additional procedures. RESULTS: 90 modified PIRS patients were matched to 90 OHRs. Patient demographics, hernia characteristics, and follow-up time were similar between the two groups after matching. There were no differences in recurrence rates (1 vs. 3 in OHR and PIRS, respectively, p = 0.6), complication rates (1 vs. 4 in OHR and PIRS, respectively, p = 0.4), and OR time [44.5 vs. 43 min in OHR and PIRS, respectively, p = 0.8]. There were no intraoperative complications for either technique. For OHR, laparoscopic look was performed in 23%. When successful, it revealed a contralateral PPV (patent processus vaginalis-PPV) in 41% of cases (9.4% of all OHR), all of which were repaired. For the PIRS procedures, a contralateral PPV was found in 25.6%, all of which were repaired. In the unmatched population, OHR had a metachronous hernia rate of 1.8%, none of whom had the contralateral PPV repaired at the original procedure. CONCLUSIONS: PIRS with peritoneal injury has comparable efficacy and good safety compared to OHR. Recurrence and complication rates should further improve with increasing experience. Future studies should elucidate long term outcomes.

Laparoscopic inguinal hernia repair in children via PIRS (percutaneous internal ring suturing).

INTRODUCTION: The miniinvasive approach is a trend in pediatric surgery nowadays. The new surgical technique called percutaneous internal ring suturing (PIRS) is a promising method bringing all the benefits of miniinvasive surgery. METHODS: Prospective study of patients operated on using the PIRS technique from 01 January 2018 to 01 January 2020 at the Department of Pediatric Surgery, 2nd Faculty of Medicine, Charles University, University Hospital Motol. RESULTS: 73 patients (25 boys and 48 girls) were operated on using PIRS. The median age was 68 months. 90 % of operations were performed by the same team of surgeons. During the procedure there were found 53 right-sided and 38 left-sided inguinal hernias. In 18 cases the hernia was bilateral, but only in 13 cases was this diagnosis made before the operation. A non-absorbable stitch was used in 57 cases to close the internal ring of the inguinal canal, and a non-absorbable monofilament in 16. The median operating time was 34 minutes. There were 3 recurrences (3.3 %) in our study.  Conclusion: In our initial study, the PIRS technique proved to be a safe alternative method to the open inguinal hernia surgery. This method provides the benefit of allowing to revise the contralateral inguinal canal as a prevention of a metachronous inguinal hernia. The cosmetic results were excellent.

Comparison of inflammatory stress response between laparoscopic and open approach for pediatric inguinal hernia repair in children.

BACKGROUND: The aim of this study was to compare inflammatory stress response between laparoscopic percutaneous inguinal ring suturing (PIRS) and open modified Marcy technique for pediatric inguinal hernia repair. METHODS: From May 2017 to April 2018, 32 male children with median age of 4.5 years undergoing inguinal hernia repair were included in randomized controlled trial. The patients were divided in two groups, by using random number generator, depending on surgical approach. The blood was tested in three time frames for white blood cells count (WBC), C-reactive protein (CRP), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RESULTS: Significant increase in concentration for all inflammatory biomarkers, that occur over time, has been found (p < 0.001 for all). Additionally, it was also found that the type of surgery significantly influenced the level of WBC, CRP, and IL-6 with Marcy showing a higher level of inflammatory response (WBC 11.4 ± 3.1 × 109/L; CRP 11.5 mg/L; IL-6 11.0 pg/mL) than the PIRS (WBC 7.6 ± 1.6 × 109/L; CRP 0.8 mg/L; IL-6 2.0 pg/mL) (p < 0.001 for all). Similar pattern was also found for TNF-α (Marcy 16.8 pg/mL; PIRS 10.1 pg/mL), but correlation between surgery type and concentration of this biomarker was significant only at the 0.1 level (p = 0.055). The mean operation time was significantly shorter (9 ± 2 min) in PIRS group compared to Marcy group (25 ± 7 min) (p < 0.001). Significantly lower median of visual analog scale score (VAS) was found in PIRS group (VAS = 2) compared to Marcy group (VAS = 6) (p < 0.001). CONCLUSIONS: Use of laparoscopic (PIRS) technique in children shows significantly lower surgical stress in comparison to open hernia repair.

Major Complication Caused by Inguinal Hernia Recurrence After Percutaneous Internal Ring Suturing Procedure in a Patient With Loeys-Dietz Syndrome: A Case Report.

Inguinal hernia repair is one of the most frequently performed procedures in pediatric surgery. Treatment methods include classical open repair and laparoscopic approach. In this report we analyze a case of a 14-month-old boy with Loeys-Dietz syndrome treated for an inguinal hernia with laparoscopic percutaneous internal ring suturing (PIRS). Two weeks post-operatively the patient was diagnosed with a recurrence of the hernia complicated by an intestine strangulation. As a re-operation of the hernia, the Lichtenstein method was applied successfully. We analyzed the literature to determine the safety and possible contradictions of the PIRS procedure, with particular emphasis on patients with comorbidities such as connective tissue disorders. We conclude that in the PIRS procedure, despite its safety, feasibility and low complication rate in healthy patients, too few studies were made to draw similar conclusions for patients with comorbidities such as connective tissue disorders.

Comparison of Percutaneous Internal Ring Suturing (PIRS) versus Open Ligation of the Patent Processus Vaginalis for the Treatment of Communicating Pediatric Hydrocele.

BACKGROUND: Although the laparoscopic approach become standard for the treatment of many surgical conditions many studies still debating whether laparoscopic surgery has significant advantages over open surgery in regards to hernia or hydrocele treatment. This study aimed to evaluate the outcomes of treatment of treatment of communicating hydrocele in pediatric patients between laparoscopic percutaneous internal ring suturing (PIRS) and open ligation of the patent processus vaginalis (PPV). METHODS: The medical records of pediatric patients who underwent surgery for communicating hydrocele between 1 January 2019 and 1 January 2024 were retrospectively reviewed. The primary objective of the study is to investigate the outcomes of treatment (complications and recurrence rates) of communicating hydrocele in children between laparoscopic and open surgical approaches. Secondary outcomes of the study are the duration of surgery and anesthesia, length of hospital stay (LOS), frequency of hospital readmissions (ReAd) and unplanned return to the operating room (uROR). RESULTS: A total of 198 children underwent surgery for a communicating hydrocele (205 repairs, as 7 cases were bilateral) and were included in the study. Of these, 87 children underwent a PIRS, while the remaining 111 cases underwent open ligation of the PPV. No recurrence of the hydrocele was observed in any of the study groups. Intraoperative complication (epigastric vein injury) was noted in two cases in both groups (2.3% vs. 1.8%, p > 0.999). A slightly higher number of postoperative complications was observed in the open group (n = 7, 6.3%) compared to the PIRS group (n = 2, 2.3%) (p = 0.190). The median duration of surgery (15 min (IQR 10, 17) vs. 21 min (IQR 15, 25); p < 0.001) and anesthesia (30 min (IQR 25, 40) vs. 40 min (IQR 35, 40); p < 0.001) were significantly lower in the PIRS group compared to open ligation of the PPV. In addition, a significantly shorter median of LOS was observed in the PIRS group compared to the open PPV group (9 h (IQR 8, 12) vs. 24 h (IQR 12, 24; p < 0.001). No cases of ReAd and uROR were observed in any of the study groups. CONCLUSIONS: PIRS is a safe and effective laparoscopic technique that can be used in the treatment of communicating hydrocele in children. PIRS showed excellent outcomes and a low incidence of complications and recurrences, comparable to traditional open surgery.

Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 ß-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor α and insulin-like growth factor-1 receptor signaling pathways.

The interaction between estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathway plays an important role in proliferation of and resistance to endocrine therapy to estrogen dependent cancers. Estrogen (E2) upregulates the expression of components of IGF-1 system and induces the downstream of mitogenic signaling cascades via phosphorylation of insulin receptor substrate-1 (IRS-1). In the present study, we evaluated the xenoestrogenic effect of bisphenol A (BPA) and antiproliferative activity of genistein (GEN) in accordance with the influence on this crosstalk. BPA was determined to affect this crosstalk by upregulating mRNA expressions of ERα and IGF-1R and inducing phosphorylation of IRS-1 and Akt in protein level in BG-1 ovarian cancer cells as E2 did. In the mouse model xenografted with BG-1 cells, BPA significantly increased a tumor burden of mice and expressions of ERα, pIRS-1, and cyclin D1 in tumor mass compared to vehicle, indicating that BPA induces ovarian cancer growth by promoting the crosstalk between ER and IGF-1R signals. On the other hand, GEN effectively reversed estrogenicity of BPA by reversing mRNA and protein expressions of ERα, IGF-1R, pIRS-1, and pAkt induced by BPA in cellular model and also significantly decreased tumor growth and in vivo expressions of ERα, pIRS-1, and pAkt in xenografted mouse model. Also, GEN was confirmed to have an antiproliferative effect by inducing apoptotic signaling cascades. Taken together, these results suggest that GEN effectively reversed the increased proliferation of BG-1 ovarian cancer by suppressing the crosstalk between ERα and IGF-1R signaling pathways upregulated by BPA or E2.

Percutaneous Internal Ring Suturing (PIRS) - The Benefits of Laparoscopic Inguinal Hernia Repair.

INTRODUCTION: The laparoscopic inguinal hernia repair in children using the PIRS technique is a well-established method. However, there are still opinions that this method does not bring more benefits than open surgery. PURPOSE: The study aims to demonstrate the benefits of laparoscopic technique over conventional, open techniques. PATIENTS AND METHODS: We conducted a retrospective study that included children aged 0-18 treated using the PIRS technique in 2008-2016. The control group consisted of patients treated with the traditional, open method of inguinal hernia repair. A total of 276 children were qualified for laparoscopic surgery, and there were 274 patients in the control group. A full laparoscopic procedure was performed on 247 patients. Assessment of the pathology of the internal inguinal ring was done in all patients during the laparoscopic procedure. Intraoperatively 79 children had bilateral inguinal hernia diagnosed, 133 right-sided inguinal herniae, and 57 left-sided inguinal herniae. The occurrence of hernia was not confirmed in 7 children, whereas 53 patients had open contralateral patent processus vaginalis. In a case of contralateral patent processus vaginalis, the repair was performed using the PIRS method. RESULTS: The recurrence of the inguinal hernia was observed in 10 children in the laparoscopic group and in 5 cases in control group. The duration of the procedure was noted and compared to open inguinal hernia repair. There was a statistically shorter duration of the laparoscopic method. In the control group, there were 16 patients with a metachronous contralateral inguinal hernia. CONCLUSION: The laparoscopic inguinal hernia repair was associated with a better assessment of hernia pathology, shorter operative time, and lower risk of contralateral hernia repair.

Percutaneous Internal Ring Suturing is a Safe and Effective Method for Inguinal Hernia Repair in Young Adolescents.

Background: Percutaneous internal ring suturing (PIRS) is a laparoscopic procedure that has demonstrated its safety and efficacy as a method of hernia repair in younger children but without evidence among the adolescent population. The aim of this study was to determine the success of PIRS outcomes for hernia repair in the adolescent population. Methods: All adolescents who were operated on using the PIRS method for inguinal repair during the 5-year study period in a single center were included in a prospective cohort study. The main outcome of the study included treatment outcomes in a term of recurrence rate. The secondary outcomes include other treatment outcomes such as complications, conversion to an open procedure, and reoperation rates, as well as duration of anesthesia and surgery, duration of hospital admission, and the level of carbon dioxide pneumoperitoneum. Results: In 51 adolescents (72.5% males) with a median age of 13 years and median follow-up of 44 months, a total of 57 PIRS procedures were performed. There were 30 (58.8%) right hernia repairs, 15 (29.4%) left hernia repairs, and 6 (11.8%) bilateral hernia repairs. The median surgical time was 10 minutes for unilateral and 18 minutes for bilateral hernia repair. The median length of hospital stay was 24 hours. Only one (1.95%) intraoperative complication occurred during surgery, an inferior epigastric vein injury. No complications or recurrences were observed during the follow-up period. Conclusions: PIRS has proven to be simple, safe, and effective method for groin hernia repair in adolescent population. This method provides excellent overall and cosmetic outcomes. There is a low incidence of complications and recurrences. According to our results, PIRS could be considered to become a possible approach for groin hernia repair in adolescents.

The Operative Time for Unilateral Inguinal Hernia Repair in Children Performed with Percutaneous Internal Ring Suturing (PIRS) or Open Approach Method.

In this study, we compared the operative time for unilateral inguinal hernia repair in children performed with either an open approach (OA) or the Percutaneous Internal Ring Suturing (PIRS) method. It was a retrospective chart review of all patients ages 0 to 18 who underwent unilateral inguinal hernia repair in the Department of Pediatric Surgery, Urology and Traumatology of the Regional Hospital in Kielce between January 2011 and December 2018. Patients with bilateral hernias or additional problems were excluded. Of 878 patients qualified for the study, 701 were in the OA group and 177 in the PIRS group. Overall, the time needed to complete the procedure was significantly longer for the OA method. The operative time was longer if the hernia was left-sided (p = 0.024). Analysis by gender showed that operative time was generally longer in males. For both genders, surgery was shorter if the PIRS method was used. For males in the PIRS group the operative time was affected by the location of the hernia, and it was longer for a left-sided hernia. The take-home message is that the PIRS procedure is faster than the OA for inguinal hernia repair in children and it might be considered as a preferred method, especially in females.

Learning Curve for Laparoscopic Repair of Pediatric Inguinal Hernia Using Percutaneous Internal Ring Suturing.

BACKGROUND: Percutaneous internal ring suturing (PIRS) is a simple and popular technique for the treatment of inguinal hernia in children. The aim of this study was to analyze the learning curves during implementation of PIRS in our department. METHODS: A total of 318 pediatric patients underwent hernia repair using the PIRS technique by three pediatric surgeons with different levels of experience in laparoscopic surgery. These patients were enrolled in a prospective cohort study during the period October 2015-January 2021. Surgical times, intraoperative and postoperative complications, in addition to outcomes of treatment were compared among the pediatric surgeons. RESULTS: Regarding operative time a significant difference among the surgeons was found. Operative time significantly decreased after 25-30 procedures per surgeon. The surgeon with advanced experience in laparoscopic surgery had significantly less operative times for both unilateral (12 (interquartile range, IQR 10.5, 16.5) min vs. 21 (IQR 16.5, 28) min and 25 (IQR 21.5, 30) min; p = 0.002) and bilateral (19 (IQR 14, 21) min vs. 28 (IQR 25, 33) min and 31 (IQR 24, 36) min; p = 0.0001) hernia repair, compared to the other two surgeons. Perioperative complications, conversion, and ipsilateral recurrence rates were higher at the beginning, reaching the benchmarks when each surgeon performed at least 30 PIRS procedures. The most experienced surgeon had the lowest number of complications (1.4%) and needed a fewer number of cases to reach the plateau. The other two surgeons with less experience in laparoscopic surgery had higher rates of complications (4.4% and 5.4%) and needed a higher number of cases to reach the plateau (p = 0.190). CONCLUSIONS: A PIRS learning curve for perioperative and postoperative complications, recurrences, and conversion rates reached the plateau after each surgeon had performed at least 30 cases. After that number of cases PIRS is a safe and effective approach for pediatric hernia repair. A surgeon with an advanced level of experience in pediatric laparoscopic surgery adopted the technique more easily and had a significantly faster learning curve.

High recurrence rate of children's inguinal hernia after percutaneous internal ring suturing: a single-center study.

AIM: To evaluate and compare the differences in recurrence rates of post inguinal hernia repair in children using Laparoscopic Intracorporeal Closure of the Processus Vaginalis (LICPV) and Percutaneous Internal Ring Closure (PIRS) operating techniques and compare them to published data. METHODS: A retrospective data analysis of children who underwent LICPV or PIRS techniques between 2005 and 2018 in the tertiary paediatric surgery department of university hospital was done. We analyzed demographic data, operating time, the influence of surgeon, recurrence rate, and the time until recurrence within an observed period of time post-operatively. RESULTS: A total of 240 patients underwent laparoscopic inguinal hernia repair procedures between 2005 and 2018. Of them 138 (57.5%) were male and 102 (42.5%) were female, with mean age of 6.48 (SD ± 4.7). LICPV method accounted for 170 (70.8%) inguinal hernia repairs, whilst 70 (29.2%) underwent the PIRS procedure. The overall recurrence rate was 8.3%; it was significantly higher in the PIRS group (18.6% versus 4.11%, p < 0.05). Males presented higher recurrence rates over females across both procedures. The mean time taken for any recurrence to happen was shorter in patients who underwent the PIRS method as opposed to LICPV techniques, 3.3 and 6.5 months, respectively (p > 0.05). CONCLUSION: In our hands, a significantly higher recurrence rate exists for children undergoing the PIRS method over LICPV techniques when treating inguinal hernias.

A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors.

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76A. After initial screening of our in-house compound library (∼2300 compounds), we identified 4 new SHP2-PTP inhibitors (0.17% hit rate) and 28 novel allosteric SHP2 inhibitors (1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP (SYK-85: IC50 = 0.32 µmol/L; WS-635: IC50 = 4.13 µmol/L) and thus represent novel scaffolds for designing new SHP2-PTP inhibitors. TK-147, an allosteric inhibitor, inhibited SHP2 potently (IC50 = 0.25 µmol/L). In structure, TK-147 could be regarded as a bioisostere of the well characterized SHP2 inhibitor SHP-099, highlighting the essential structural elements for allosteric inhibition of SHP2. The principle underlying the cross-validation protocol is potentially feasible to identify allosteric inhibitors or those inactivating mutants of other proteins.

Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management.

Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.

Raspberry ketone and Garcinia Cambogia rebalanced disrupted insulin resistance and leptin signaling in rats fed high fat fructose diet.

AIM: Obesity is a continually growing pandemic leading to many diseases that affect the overall quality of life. The widely marketed Garcinia cambogia (GC) and Raspberry ketone (RK) were used in this study. Despite their known dietetic effect, however, the metabolomic/signaling pathways involved in this effect are not fully elucidated. Hence, our study comprehends the possible trajectories of their combination against obesity and insulin resistance in addition to exploring their combination merit. MATERIALS AND METHODS: Adult male Wistar rats were divided into 5 groups; viz., normal diet (ND), high fat fructose diet (HFFD), HFFD+GC (600mg/kg), HFFD+RK (55mg/kg) and HFFD+GC+RK. To assess our aim, we determined their effect on body weight, IPGTT, glucose homeostasis (glucose, insulin, HOMA IR), lipid profile parameters and SREBP-1c, oxidative stress markers, insulin and leptin signaling pathways (p-IRS-1/p-AKT/GLUT-4, and leptin/STAT-3), as well as liver and adipose tissue histopathology. RESULTS: GC/RK combinationcaused weight loss, corrected the disturbed glucose and insulin homeostasis, raised serum levels of HDL anddecreased all other lipid profile parameters. They also increased Nrf-2 expression, ad GSH, as well as p-IRS-1/p-Akt/GLUT-4 cue, while they decreased MDA, leptin/STAT-3 and SREBP-1c content compared to the HFFD group. Furthermore, the GC/RK combination abolished apoptosis, fatty changes and inflammation in hepatocytes and decreased sclerotic blood vessels and congestion in adipose tissue. CONCLUSION: Our study highlights the involvement ofp-IRS-1/p-Akt/GLUT-4, leptin/STAT-3 and SREBP-1c signaling trajectories in the beneficial combination of GC and RK, besides, the efficient rebalance of the redox status, insulin resistance and tissue fat deposition confirmed histopathologically.

Silibinin ameliorates hepatic lipid accumulation and oxidative stress in mice with non-alcoholic steatohepatitis by regulating CFLAR-JNK pathway.

Non-alcoholic steatohepatitis (NASH) is a chronic metabolic syndrome and the CFLAR-JNK pathway can reverse the process of NASH. Although silibinin is used for the treatment of NASH in clinical, its effect on CFLAR-JNK pathway in NASH remains unclear. This study aimed to investigate the effect of silibinin on CFLAR-JNK pathway in NASH models both in vivo and in vitro. The in vivo study was performed using male C57BL/6 mice fed with methionine- choline-deficient diet and simultaneously treated with silibinin for 6 weeks. The in vitro study was performed by using mouse NCTC-1469 cells which were respectively pretreated with oleic acid plus palmitic acid, and adenovirus-down Cflar for 24 h, then treated with silibinin for 24 h. After the drug treatment, the key indicators involved in CFLAR-JNK pathway including hepatic injury, lipid metabolism and oxidative stress were determined. Silibinin significantly activated CFLAR and inhibited the phosphorylation of JNK, up-regulated the mRNA expression of Pparα, Fabp5, Cpt1α, Acox, Scd-1, Gpat and Mttp, reduced the activities of serum ALT and AST and the contents of hepatic TG, TC and MDA, increased the expression of NRF2 and the activities of CAT, GSH-Px and HO-1, and decreased the activities and expression of CYP2E1 and CYP4A in vivo. These effects were confirmed by the in vitro experiments. Silibinin prevented NASH by regulating CFLAR-JNK pathway, and thereby on one hand promoting the ß-oxidation and efflux of fatty acids in liver to relieve lipid accumulation, and on the other hand inducing antioxidase activity (CAT, GSH-Px and HO-1) and inhibiting pro-oxidase activity (CYP2E1 and CYP4A) to relieve oxidative stress.

Effects of Ji Tang Zhi on glucose metabolism and related protein expression in insulin resistance HepG 2 cell line / 药物评价研究

Objective To evaluate the effect of Ji Tang Zhi on glucose metabolism in insulin resistance (IR) HepG 2 cell line,and to explore the related mechanism.Methods The HepG2 cells were incubated in culture medium addition of 10-7 mol/L insulin for 24 h to establish the IR cell model.Effect of Ji Tang Zhi on rate of glucose absorption in HepG2 cell was detected by the method of glucose oxidase-peroxidase (GOD-POD).We performed an MTT assay to determine cytotoxicity effects of Ji Tang Zhi on HepG2 cell line.The expression of p-IRS-1 Ser307,PI3K and GLUT-4 were detected by Western blotting.Results Incubated with 10-7 mol/L insulin for 24 h,the insulin resistance cell model had been built.Compared with model group,the rate of glucose absorption of cell treated with JTZ (30 ～ 120 μg/mL) was significantly improved.According to model cells,the expression of GLUT-4 and PI3K decreased significantly compared to control cells.While the expression of p-IRS-1 Ser 307 was inhibited and GLUT-4 and PI3K expression were increased in IR cells after treated with JTZ (30 ～ 120 μtg/mL).Conclusion JTZ exert beneficial effects on hyperglycosemia in IR cell line possibly through regulating the levels of GLUT-4,p-IRS-1 Ser307 and PI3K in HepG2 cell.

Remoción anaerobia del colorante azul directo brl en Reactor Anaerobio de Flujo Ascendente UASB (Upflow Anaerobic Sludge Blanket) con carbón activado / Anaerobic removal of the brl direct blue dye in Upflow Anaerobic Sludge Blanket (UASB) with activated carbon

En esta investigación se utilizó el colorante azul directo brl para remoción anaerobia con un consorcio bacteriano aislado de efluentes industriales del Parque Industrial río Seco (PIRS), Arequipa, Perú; en un reactor anaerobio de flujo ascendente UASB con carbón activado. El reactor tuvo una capacidad de 14.4 L con lodos y carbón activado del 40% de volumen, con una carga orgánica de 6 Kg DQO/m³•día y un tiempo de retención hidráulica de 1 día con un flujo ascendente. El objetivo fue medir la eficiencia de la remoción anaerobia del colorante en un tiempo de 28 días. Los resultados demostraron un incremento del 41% de los Sólidos Suspendidos Volátiles (SSV) de 12894 mg•L-1 a 21546 mg•L-1 bajo las condiciones del experimento, con una remoción del 57% de la Demanda Química de Oxigeno (DQO) de 484 mg•L-1 a 122 mg•L-1 y una remoción del 87% del colorante azul directo brl de 69.61 mg•L-1 a 9 mg•L-1. Los resultados con el carbón activado granular solamente, demostraron una remoción del 61% del colorante azul directo brl de 70.67 mg•L-1 a 27.83 mg•L-1 a los 28 días.

In this research the brl direct blue dye was used for anaerobic removal with a bacterial consortium of industrial effluents from Industrial Park Río Seco (IPRS), Arequipa, Peru; in an anaerobic reactor of UASB Upflow with activated carbon. The reactor had a capacity of 14.4 L with sludge and activated carbon of 40% of volume, with an organic load of 6 Kg COD/m³•dia and a hydraulic retention time of 1 day with an upward flow. The objective was to measure the efficiency of the anaerobic removal of coloring in a time of 28 days. The results showed an increase of 41% of the solids suspended volatile (SSV) 12894 mg•L-1 up to 21546 mg•L-1 under the conditions of the experiment, with a removal of 57% of the chemical demand of oxygen (COD) from 484 mg•L-1 to 122 mg•L-1 and a removal of 87% of the dye Blue direct the 69.61 brl mg•L-1 to 9 mg•L-1. Results with activated charcoal granular only, they showed a removal of 61% of the dye Blue direct 70.67 brl mg•L-1 to 27.83 mg•L-1 at 28 days.