Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Progress of Rhei Radix et Rhizoma and Its Combination in Treatment of Cerebral Hemorrhage： A Review / 中国实验方剂学杂志

Cerebral hemorrhage accounts for about 10%-15% of all strokes， and its pathogenesis is complex. Currently， the main clinical treatment is mainly medical symptomatic treatment， including the use of antihypertensive drugs， hypoglycemic drugs， and hemostatic drugs， and surgical treatment is required in some cases， but there is still a lack of effective treatment. In recent years， traditional Chinese medicine and proprietary Chinese medicine have been widely accepted for their stable efficacy， high safety， and low cost. Rhei Radix et Rhizoma is one of the most commonly used herbal medicines for the treatment of cerebral hemorrhage. This paper summarizes the relevant literature on the treatment of cerebral hemorrhage with Rhei Radix et Rhizoma and finds that its active ingredients are mainly anthraquinones， such as emodin， Rhei Radix et Rhizoma acid， and Rhei Radix et Rhizoma phenol. The herbal formulas are Da Chengqitang， Shengdi Dahuangtang， Liangxue Tongyufang， and Naoxueshu oral liquid. The effects involve protecting the blood-brain barrier， promoting hematoma absorption， reducing inflammation levels， decreasing lactic acid accumulation at the bleeding site， and increasing the expression of brain-derived neurotrophic factors. The pathways involved include aquaporin 4 （AQP4）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， Toll-like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB）， nuclear factor E2-related factor 2 （Nrf2）， and Wnt3a/β-linked protein pathway. This paper summarizes the progress of clinical studies and animal experiments on the treatment of cerebral hemorrhage with active ingredients of Rhei Radix et Rhizoma and herbal compounds containing Rhei Radix et Rhizoma， so as to provide a reference for the treatment protocol of cerebral hemorrhage.

A framework of the influencing factors of the therapeutic effect of Tuina treatment on pain based on the Delphi method / 国际中医中药杂志

Based on the resutls of literature review and interviews of experts, two rounds of Delphi surveys were conducted. The mean, importance ratio, coefficient of variation and coordination coefficient were used for assessment of survey from multiple perspectives, and finally form a framework model of factors affecting the efficacy of Tuina therapy. A total of 37 experts were selected for questionnaire surveys, the positive coefficients of experts' participatation in the first round and second round were 92.5% and 80.0%, respectively. The overall coordination coefficient in the second round is 0.68. The items were included into the consensus meeting if the importance ratio of items were equal to and more than 80%. After the expert consensus meeting, 22 items were included to form a framework model of factors affecting the efficacy of Tuina therapy, and summarized as 5 major influencing factors, including diagnostic factors, treatment factors, prognostic factors, patient factors, and doctor-patient communication. This framework can guide and help young Tuina practitioners to improve clinical efficacy. It is also clearly pointed out that the effect of Tuina for pain is not only related to disease diagnosis or manipulation, but also related to home exercise, health care, and doctor-patient communication.

An All-in-One, Bioderived, Air-Permeable, and Sweat-Stable MXene Epidermal Electrode for Muscle Theranostics.

Muscle fatigue is a common symptom experienced by many people and associated with less maximal force production of fatigued muscle. It is highly desirable to simultaneously and imperceivably diagnose muscle fatigue and restore muscle function using one skin electrode, yet no such electrode has been developed so far. Herein, we report an all-in-one, bioderived, air-permeable, and sweat-stable MXene electrode that can concurrently and comfortably record electromyographic (EMG) signals and achieve electrostimulation and electrothermal therapy for muscle theranostics. Leveraging the structural arrangement of perennial herbs and ion cross-linking of MXene in sweat, MXene-based electrodes (MBE) exhibit high breathability, are ultralightweight (∼0.25 mg/cm3), and have low and stable electrode-skin interfacial impedance at a variety of environments, facilitating the long-term reliable monitoring of electrophysiology. Taken together with electrostimulation and electrothermal therapy at the skin surface, MBE can diagnose muscle fatigue and restore muscle function by stimulating blood circulation. In addition, it can also be used for muscle rehabilitation training and prosthesis control via human-computer interaction. Our all-in-one, bioderived, air-permeable, and sweat-stable MXene electrode has a great potential for daily wearable healthcare of muscle fatigue.

[Warming acupuncture combined with moxibustion at Yongquan (KI 1) for knee osteoarthritis with kidney-marrow deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect between warming acupuncture combined with moxibustion at Yongquan (KI 1) and simple warming acupuncture for knee osteoarthritis with kidney-marrow deficiency. METHODS: A total of 66 patients of knee osteoarthritis with kidney-marrow deficiency were randomized into an observation group and a control group, 33 cases in each one. Warming acupuncture was applied at Neixiyan (EX-LE 4), Dubi (ST 35), Zusanli (ST 36) and Xuanzhong (GB 39) on the affected side in both of the groups. In the observation group, mild moxibustion at bilateral Yongquan (KI 1) was adopted additionally. Each treatment lasted for 30 min, 3 times a week (once every other day), and the consecutive 6 weeks of treatment were required. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (such as joint pain, stiffness and physical function), the amount of joint effusion and the serum contents of interleukin-1ß(IL-1ß), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) were observed before and after treatment in the two groups. RESULTS: The total effective rate in the observation group was 93.3% (28/30), which was superior to 87.1% (27/30) in the control group (P<0.05). Compared before treatment, the pain scores, stiffness scores, physical function scores, the amount of joint effusion and the contents of IL-1ß, TNF-α and hs-CRP after treatment were significantly reduced in the two groups (P<0.05), and the improvements of these indices in the observation group were superior to the control group (P<0.05). CONCLUSION: Warming acupuncture combined with moxibustion at Yongquan (KI 1) can improve joint function, reduce the amount of joint effusion and the contents of inflammatory response indices for knee osteoarthritis with kidney-marrow deficiency. The therapeutic effect of warming acupuncture combined with moxibustion at Yongquan (KI 1) is better than simple warming acupuncture.

Curcumin Promotes Apoptosis of Activated Hepatic Stellate Cells by Inhibiting Protein Expression of the MyD88 Pathway.

Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway. HSC (rat HSC T6) were divided into a control group, MyD88 small interfering RNA (siRNA) group, curcumin group, and curcumin + MyD88 siRNA group. The MyD88 siRNA groups were exposed to siRNA for 48 h. The curcumin groups were cultured in the presence of curcumin for 24 h. Apoptosis was detected by flow cytometry. For Toll-like receptor (TLR) 2 and 4 as well as MyD88 and the dependent factors NF-κB, TNF-α, and IL-1ß, mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). For MyD88, protein expression was further observed by Western Blot. Both curcumin and MyD88 siRNA inhibited the mRNA expression of MyD88 pathway-related effectors (TLR2, TLR4, NF-κB, TNF-α, IL-1ß) in HSC. Furthermore, both treatments reduced the expression of MyD88 protein in HSC and promoted their apoptosis. These effects were more obvious in the curcumin + MyD88 siRNA group. This study demonstrates that curcumin promotes apoptosis of activated HSC by inhibiting the expression of cytokines related to the MyD88 pathway. It elucidates the possible mechanisms of curcumin in inducing apoptosis of HSC through the MyD88 pathway.

Effect of Telbivudine Tablet Combined Jianpi Bushen Recipe on HBV Specific Cytotoxic T Lymphocyte and HBeAg Seroconversion in Patients with HBeAg Positive Chronic Hepatitis B / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Telbivudine (LDT) Tablet combined with Jianpi Bushen Recipe (JBR) on serum hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) and HBeAg seroconversion in chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Totally 90 HBeAg-positive and human leukocyte antigen (HLA)-A2 positive CHB patients were randomly assigned to the treatment group and the control group, 45 cases in each group. Patients in the treatment group took LDT Tablet (600 mg, once per day) combined with JBR granule (twice per day), while those in the control group took LDT Tablet alone. The therapeutic course for all was one year. HBV DNA negative conversion rate, HBeAg seroconversion rate, and level of HBV specific CTL were compared after 1 year treatment; liver function, drug resistance mutations, and adverse reactions were also compared between the two groups.</p><p><b>RESULTS</b>After 1 year treatment, HBV DNA negative conversion rate and HBeAg seroconversion rate were 88.89% (40/45) and 40.00% (18/45) in the treatment group, higher than those of the control group [68.89% (31/45) and 20.00% (9/45)], with statistical difference (P < 0.05). Level of HBV specific CTL in the treatment group was 0.78% +/- 0.09% after treatment, higher than that of the control group after 1 year treatment (0.54% +/- 0.11%) and that before treatment (0.36% +/- 0.07%), with statistical difference (P < 0.01). Level of HBV specific CTL in 27 patients with HBeAg seroconversion was 0.81% 0.10%, higher than that of 63 patients without HBeAg seroconversion (0.60% +/- 0.09%), with statistical difference (P < 0.01). ALT returned to normal in 44 cases of the treatment group (97.78%), while it was 42 cases (93.33%) of the control group, with no statistical difference between the two groups (P > 0.05). Total bilirubin (TBil) in the two groups all turned to normal. rtM204I variation occurred in 1 case (2.22%) of the treatment group and 2 cases (4.44%) in the control group. No obvious adverse reaction occurred in the two groups.</p><p><b>CONCLUSION</b>LDT Tablet combined with JBR could elevate levels of HBV specific CTL and HBeAg seroconversion in CHB patients.</p>

Treatment of early and mid-term primary biliary cirrhosis by Qingying Huoxue Decoction Combined ursodeoxycholic acid: a clinical observation / 中国中西医结合杂志

<p><b>UNLABELLED</b>OBJECTIVE To observe the clinical efficacy by Qingying Huoxue Decoction (QHD) combined ursodeoxycholic acid (UDCA) in treating patients with early and mid-term primary biliary cirrhosis (PBC). METHODS Totally 78 patients were randomly assigned to the treatment group and the control group, 39 in each group. All patients received basic treatment and took UDCA (at the daily dose of 13-15 mg/kg). Patients in the treatment group took QHD, one dose per day. The treatment course for all was 6 weeks. Clinical efficacy, gamma-glutamyl transferase (γ-GGT), alkaline phospatase (ALP), TBIL, alanine aminotransferase (ALT), and aspartate transaminase (AST) were observed before and after treatment. RESULTS Totally 21 (53. 8%) patients obtained complete response in the treatment group, with statistical difference when compared with that of the control group (11 cases, 30. 8%). Levels of GGT, ALP, ALT, AST, and TBIL decreased in the two groups after treatment (P < 0.01). Levels of ALP, GGT, and TBIL were obviously lower in the treatment group than in the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>QHD combined UDCA in treating early and mid-term PBC patients was superior to the effect of using UDCA alone. It also could improve patients' liver function.</p>

Effect of compound qizhu granule on cellular immunity of chronic hepatitis B patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of compound qizhu granule (CQG) on cellular immunity of chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Totally 103 CHB patients treated with lamivudin (LAM) for 6 months, who had partial virological response (HBeAg positive) were randomly assigned to two groups, 50 in the treatment group and 53 in the control group. All patients took LAM 100 mg (once a day) plus ADV 10 mg (once a day). Patients in the treatment group additionally took CQG, one dose per day. After one-year treatment hepatitis B virus (HBV) DNA negative rates, HBeAg seroconversion, levels of HBV specific cytotoxic T lymphocyte (CTL), non-specific CTL and natural killing (NK) cells were compared between the two groups.</p><p><b>RESULTS</b>After 1-year treatment, HBV DNA negative rate of the treatment group was 88: 0% in 44 cases, slightly higher than that of the control group (41 cases, 77.4%), but with no statistical difference (P >0.05). HBeAg seroconversion of the treatment group was 32.0% in 16 cases, higher than that of the control group (8 cases, 15.1%), with statistical difference (P <0.05). Levels of HBV specific CTL (0.79%±0. 07%), non-specific CTL (19.4%±1.8%) and NK cells (14. 1%± 1.5%) of the treatment group were higher than those of the control group (0.58% ± 0.08%, 17.5% ± 1.7%, and 11.1%±1.5%, respectively; allP <0.01).</p><p><b>CONCLUSION</b>Treating CHB patients with partial virological response by ADV plus CQG could improve specific and non-specific cellular immunity, thereby elevating HBeAg seroconversion rate.</p>

Optimization of formulas of Quban gel by uniform design / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize formulas of Quban gel.</p><p><b>METHOD</b>The U6 (6(2) x 3) uniform design was adopted to optimize gel formulas, with rheological parameters, such as viscosity and yield value in room temperature, viscosity and yield value in average temperature of skin, thixlotropy.</p><p><b>RESULT</b>The optimum proportion of matrix was made of 1.0 g carbomer 940, 5 mL glycerin and pH value 5-6.</p><p><b>CONCLUSION</b>The regression model for gel matrix quality and gel rheological parameters was established to directly reflect the impacting effect of various factors, and provide certain preference basis for the screening of gel matrix formulas. Quban gel prepared by the method was evenly distributed, moderately viscous and highly thixotropic</p>

Prognostic prediction of BRAF(V600E) and its relationship with sodium iodide symporter in classic variant of papillary thyroid carcinomas.

BACKGROUND: The aim of this study was to evaluate the prognosis of the classic variant of papillary thyroid carcinomas with the BRAF(V600E) mutation and 131I treatment failure in those tumors due to lower functional sodium iodide symporter expression. METHODS: 109 papillary thyroid carcinomas were associated with clinicopathologic features. The BRAF(V600E) mutation was evaluated by direct sequencing and sodium iodide symporter protein was determined by immunohistochemistry. RESULTS: We found that the BRAF(V600E) mutation was significantly associated with the classic variant of papillary thyroid carcinomas and was independent of tumor size, the presence of extrathyroid invasion and lymph node metastasis, advanced TMN stages, and a high risk of disease recurrence. Moreover, the BRAF(V600E) mutation was associated with a statistically significant lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. However, those statistically significant relationships were not found in the follicular variant of papillary thyroid carcinomas. CONCLUSIONS: The BRAF(V600E) mutation might be associated with a more aggressive phenotype and a poor prognosis, causing less NIS-mediated 131I uptake due to a lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. Our current study appears to be valuable for predicting prognosis and is of important clinical significance for surgery and 131I treatment in patients with the classic variant of papillary thyroid carcinomas.

Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes simplex virus production method.

Recombinant adeno-associated virus (rAAV) vectors offer promise for gene therapy of alpha-1 antitrypsin (AAT) deficiency. A toxicology study in mice evaluated intramuscular injection of an rAAV vector expressing human AAT (rAAV-CB-hAAT) produced using a herpes simplex virus (HSV) complementation system or a plasmid transfection (TFX) method at doses of 3 × 10(11) vg (1.2 × 10(13) vg/kg) for both vectors and 2 × 10(12) vg (8 × 10(13) vg/kg) for the HSV-produced vector. The HSV-produced vector had favorable in vitro characteristics in terms of purity, efficiency of transduction, and hAAT expression. There were no significant differences in clinical findings or hematology and clinical chemistry values between test article and control groups and no gross pathology findings. Histopathological examination demonstrated minimal to mild changes in skeletal muscle at the injection site, consisting of focal chronic interstitial inflammation and muscle degeneration, regeneration, and vacuolization, in vector-injected animals. At the 3 × 10(11) vg dose, serum hAAT levels were higher with the HSV-produced vector than with the TFX-produced vector. With the higher dose of HSV-produced vector, the increase in serum hAAT levels was dose-proportional in females and greater than dose-proportional in males. Vector copy numbers in blood were highest 24 hr after dosing and declined thereafter, with no detectable copies present 90 days after dosing. Antibodies to hAAT were detected in almost all vector-treated animals, and antibodies to HSV were detected in most animals that received the highest vector dose. These results support continued development of rAAV-CB-hAAT for treatment of AAT deficiency.

[Preliminary study on mechanism of therapeutic effect of Huganjiexian decoction on hepatic fibrosis].

OBJECTIVE: To observe the effects of Huganjiexian decoction on rat hepatic fibrosis and the creation of cytokines. METHODS: Rat hepatic fibrosis was induced by intraperitoneally injection of carbon tetrachloride. At the same time, these rats were treated with different dosages of Huganjiexian decoction. Sho-saiko-to compound treating group and Fufangbiejiarangan Tablets treating group were used as positive controls. After twelve weeks, all rats were executed. Histopathologic changes were observed after H.E and Masson stainings. The expression of collagen type I, collagen type III, TGF-beta 1 and PDGF-BB in liver were detected by immunohistochemical staining. RESULTS: Compared with fibrotic group, hepatic fibrosis in decoction groups was significantly improved. In decoction groups, levels of collagen type I, collagen type III, TGFbeta1 and PDGF-BB were decreased, especially in the low-dose curcumin group. The TGF-beta 1 positive percentage were 7.56%+/-2.18%, 29.25%+/-7.84%, 13.54%+/-4.15%, 21.82%+/-6.64%, 20.06%+/-7.14%, 13.78%+/-4.35%, 12.75%+/-3.98% in liver tissues from normal group, model group, low, middle, high curcumin, Sho-saiko-to compound and Fufangbiejiarangan Tablets treating groups respectively (P less than 0.05); while the PDGF-BB positive percentage were 1.68%+/-0.41%, 11.70%+/-2.28%, 3.65%+/-0.76%, 5.24%+/-1.04%, 6.37%+/-1.12%, 4.16%+/-0.61%, 3.38%+/-0.56% in liver tissues from those groups respectively (P less than 0.05). CONCLUSION: Huganjiexian decoction can improve rat hepatic fibrosis, possibly via inhibiting the expression of collagen type I, collagen type III, TGFbeta1 and PDGF-BB.

Neoadjuvant chemotherapy followed by concurrent chemoradiation for locally advanced nasopharyngeal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Concurrent chemoradiation therapy (CCRT) is the standard treatment for patients with locally advanced nasopharyngeal carcinoma (NPC). The effect of neoadjuvant chemotherapy followed by CCRT has not been determined. Therefore, we conducted 2 phase II studies to evaluate the efficacy and safety of neoadjuvant chemotherapy with a regimen of docetaxel, cisplatin, and 5 fluorouracil (5-Fu) (TPF) followed by radiotherapy and concurrent cisplatin in patients with stage III and IV(A - B) NPC. This article is the preliminary report on treatment related toxicities and response.</p><p><b>METHODS</b>Graded according to the 2002 American Joint Committee on Cancer (AJCC) staging criteria, only patients with stage III or IV(A-B) poorly differentiated or undifferentiated NPC (World Health Organization type II/III) were included. We planned to recruit 52 patients with stage III disease and 64 patients with stage IV(A - B) disease. All patients received neoadjuvant chemotherapy with TPF (docetaxel 75 mg/m(2), day 1; cisplatin 75 mg/m(2), day 1; 5 Fu 500 mg/(m2 x day), continuous intravenous infusion for 120 h), every 3 weeks for 3 cycles, followed by weekly cisplatin (40 mg/m(2)) concurrent with radiotherapy. Three dimensional conformal radiotherapy (3D CRT) and intensity modulated radiotherapy (IMRT) were used. Gross disease planning target volume (PTV), high risk and low risk subclinical PTV doses were prescribed at 70-76 Gy, 66-70 Gy, and 60-61.25 Gy at 1.75-2.0 Gy per fraction. The lower neck or supraclavicular fields may be treated with conventional AP/PA fields for a total of 54 Gy at 1.8 Gy per fraction. Patients were evaluated for tumor response after the completion of neoadjuvant chemotherapy, and at 3 months after radiation according to the Response Evaluation Criteria In Solid Tumors (RECIST). The latest version of the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE 3.0) was used for grading all adverse events.</p><p><b>RESULTS</b>Fifty nine patients were evaluable for treatment response. Thirty patients had stage III disease and 29 patients had stage IV(A-B). All patients completed RT to the prescribed dose and 2 cycles of neoadjuvant chemotherapy, with 51 patients (86.4%) completing 3 cycles. A total of 50 (84.7%) and 39 patients (66.1%) completed 4 weeks and 5 weeks of cisplatin during CCRT, respectively. The overall response rate in the primary site and the neck region were 94.9% [complete response (CR) in 25.4%] and 100% (CR in 19.6%) after completing neoadjuvant chemotherapy. At 3 months after RT, the CR rates increased to 96.6% and 90.2%, respectively. After a median follow up of 14.3 months, we observed 5 treatment failures and 2 deaths. The 1 year overall survival, distant metastasis free survival, and locoregional relapse free survival rates were 100%, 95.7%, and 97.7%, respectively. The rates of grade 3/4 myelosuppression and anorexia/nausea/vomiting during neoadjuvant chemotherapy were 55.9% and 16.9%, respectively. The corresponding rates were 11.9% and 23.7% during CCRT. Grade 3/4 mucositis, skin desquamation, and xerostomia occurred in 6.8%, 44.1%, and 27.1% of patients, respectively. There were no treatment related deaths.</p><p><b>CONCLUSIONS</b>Neoadjuvant chemotherapy with TPF followed by CCRT was well tolerated with a manageable toxicity profile. Preliminary results are encouraging and warrant further investigation.</p>

Synthesis and herbicidal activity of isoindoline-1,3-dione substituted benzoxazinone derivatives containing a carboxylic ester group.

A carboxylic ester group was introduced to three series of isoindolinedione substituted benzoxazinone derivatives. Some of these analogues exhibited good herbicidal activities, and the injury symptoms against weeds included leaf cupping, crinkling, bronzing, and necrosis, typical of protox inhibitor herbicides. Structurally, they were classified as Chemical Group A (4-carboxylic ester group-6-isoindolinyl-benzoxazinones), B (4-carboxylic ester group-7-isoindolinyl-benzoxazinones), and C (4-carboxylic ester group-6- tetrahydroisoindolinyl-benzoxazinones). All of the tested compounds were structurally confirmed by (1)H NMR, IR, mass spectroscopy, and elemental analysis. Preliminary bioassay data of these three classes of compounds showed that, in general, the order of the herbicidal effectiveness is C > A > B. Several of the lead compounds, for example, C10 (methyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2-methyl-3-oxo-2H-benzo[b][1,4] oxazin-4(3H)-yl) propano-ate), C12 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2- methyl-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) propanoate), and C13 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2-methyl-3-oxo-2H-benzo-[b][1,4]oxazin-4(3H)-yl) butanoate), exhibited greater than 80% control at 75 g a.i./ha in both pre- and postemergence treatments against dicotyledonous weeds, such as Abutilon theophrasti Medic, Chenopodium album L., and Amaranthus ascendens L., and monocotyledon weeds, such as Digitaria sanguinalis L., Echinochloa crus-galli L., and Setaria viridis L. On the basis of advanced screening tests and crop selectivity, compounds C10, C12, and C13 are safer to crops than flumioxazin. Compounds C10, C12, and C13 are potent to develop as pre-emergent herbicides used in peanut, soybean, maize, and cotton fields.

Curcumin prevents liver fibrosis by inducing apoptosis and suppressing activation of hepatic stellate cells.

This study was designed to investigate the prophylactic effects and the mechanisms of curcumin on liver fibrosis in rats. Liver fibrosis was induced in 72 Sprague Dawley rats by intraperitoneal injection of carbon tetrachloride. Rats were divided into control, liver fibrosis, high, medium, and low dose curcumin (200, 100, and 50 mg kg(-1), respectively), and colchicine (0.1 mg kg(-1)) groups. After 8 weeks of treatment, histopathological examination was performed on hepatic tissues, and liver fibrosis was graded. Hepatic stellate cells activity was examined by smooth muscle alpha-actin immunohistochemistry staining, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling. The liver fibrosis score in the high, medium, and low dose curcumin group (5.79 +/- 1.80, 8.58 +/- 3.34, and 9.58 +/- 3.32, respectively) and the colchicine group (4.91 +/- 1.28) was significantly lower than in the fibrosis group (20.40 +/- 3.38, P < 0.01). The ratio of activated hepatic stellate cells in the three curcumin groups (0.97 +/- 0.69, 2.06 +/- 0.58, and 3.49 +/- 1.03, respectively) and the colchicine group (0.78 +/- 0.31) was significantly lower than in the fibrosis group (6.08 +/- 1.13, P < 0.05). The apoptosis index in the three curcumin groups (0.57 +/- 0.21, 0.37 +/- 0.22, and 0.34 +/- 0.21, respectively) was higher than in the fibrosis (0.09 +/- 0.09, P < 0.05) or the colchicine group (0.16 +/- 0.19, P < 0.05). Curcumin prevents carbon tetrachloride-induced liver fibrosis in rats. The prevention of liver fibrosis may be due to the inhibition of the activation of hepatic stellate cells and induction of their apoptosis.

[Therapeutic effects of curcumin treatment on hepatic fibrosis].

OBJECTIVE: To investigate the therapeutic effects and mechanisms of curcumin treatment on hepatic fibrosis. METHODS: A model of hepatic fibrosis was established using carbon tetrachloride intraperitoneal injections in rats. Curcumin was administered to one group of the model rats (curcumin group) and the other rats were used as controls (control group). Serum levels of ALT, AST, HA, LN, PCIII, and NO were measured, and Hyp, MDA, and SOD in liver tissues were measured. Liver tissue slides were stained with HE and Masson staining to study the pathological changes in the livers. Grades of hepatic fibrosis were evaluated according to a semiquantitative scoring system. RESULTS: In the curcumin group, serum levels of ALT, AST, NO, HA, LN, PCIII, MDA, and Hyp, were (218.50+/-48.89) U/L, (376.60+/-79.13) U/L, (47.96+/-6.53) micromol/L, (289.96+/-60.43) mg/L, (107.35+/-27.24) mg/L, (148.95+/-28.63) microg/L, (236.10+/-30.54) nmol/g, (478.40+/-75.74) microg/g and all were lower than those of the control group (693.75+/-117.57) U/L, (892.50+/-105.69) U/L, (70.95+/-10.23) micromol/L, (468.22+/-93.45) mg/L, (346.44+/-75.08) mg/L, (279.82+/-54.00) microg/L, (402.25+/-39.16) nmol/g, and (752.50+/-77.62) microg/g. The differences were significant. In the curcumin group, the level of SOD (90.39+/-21.23) in the liver tissues was significantly higher than that of the control group (46.52+/-20.01). The hepatic fibrosis scores in the curcumin group were significantly lower than those of the control group. These effects were dose-dependent. CONCLUSIONS: Curcumin reduces rat hepatic fibrosis. Anti-peroxidation and regulation of collagen metabolism in liver tissues may be involved in the therapeutic effectiveness of curcumin on hepatic fibrosis.

[The study of therapeutic effects of curcumin on hepatic fibrosis and variation of correlated cytokine].

OBJECTIVE: To investigate therapeutic effects of curcumin on hepatic fibrosis and the variation of correlated cytokine. METHODS: Rat models of hepatic fibrosis were made by carbon tetrachloride. Curcumin of 10, 20, 40 mg per 100 gram weight of rat were given to these rats of curcumin group respectively from ninth week. Normal, dissolvent, model and Salvia miltiorrhiza groups were made as controls. Serum levels of ALT, AST, HA, LN, PC-III were detected; Serum levels of TGF-beta1 and TNF-alpha were detected by ELISA method; Serum levels of NO were detected by chemical method. HE and Masson staining were conducted in hepatic tissues to observe pathological variations. Grades of hepatic fibrosis were evaluated according to SSS system. Immunohistochemical staining was executed for detecting PDGF-BB in liver, and professional software for image analysis was used. RESULTS: Curcumin could decrease serum levels of ALT, AST, HA, LN, PC-III obviously, P < 0.05, which were increased in fibrotic group. Curcumin could decrease cytokine levels of NO, TGF-beta1, TNF-alpha, P < 0.05. Curcumin could obviously improve liver pathological variations of fibrotic rats. The score of hepatic fibrosis in curcumin group reduced significantly, P < 0.05. Curcumin treatment could reduce the expression of PDGF-BB, P < 0.05. These effects were dose-dependent. CONCLUSION: Curcumin can heal rat hepatic fibrosis. Effects of reducing the expression of correlated cytokines may be mechanisms of therapeutic effects of curcumin on hepatic fibrosis.