Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011-2016.

Background: Over the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated. Similarly, there is a dearth of research on the correlation between serum apolipoprotein B (apoB) and serum total testosterone (TT), particularly within specific populations. Methods: We conducted a cross-sectional study to assess the relationship between serum TT concentration and serum apoB concentration. Using the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, we employed weighted generalized linear models, weighted univariate, weighted multivariate analysis, and smooth curve fitting to assist in exploring the relationship between serum TT and apoB. Serum apoB concentration served as the independent variable, and serum TT concentration as the dependent variable. ApoB was divided into four quartiles-Q1 (<0.7g/L, N=691), Q2 (≥0.7g/L to <0.9g/L, N=710), Q3 (≥0.9g/L to <1.1g/L, N=696), and Q4 (≥1.1g/L, N=708)-thereby further solidifying the stable association between the two. Additionally, the application of smooth curve fitting will contribute to a more detailed elucidation of the specific relationship between serum TT concentration and serum apoB concentration under different factors (Drinking, Smoke, Diabetes, Hypertension, and High cholesterol level.). Results: The results indicate a negative correlation between serum TT concentration and apoB concentration (ß=-113.4; 95% CI: -146.6, -80.2; P<0.001). After adjusting for confounding variables, the negative correlation between apoB concentration and TT concentration remains significant (ß=-61.0; 95% CI: -116.7, -5.2; P=0.040). When apoB concentration was converted from a continuous variable to a categorical variable (quartiles: Q1<0.7g/L; Q2:≥0.7g/L to<0.9g/L; Q3:≥0.9g/L to <1.1g/L; Q4: ≥1.1g/L), TT level of participants in the highest quartile (≥1.1g/L) was -47.2 pg/mL (95% CI: -91.2, -3.3; P=0.045) lower than that in the lowest quartile (<0.7g/L). The smooth curve fitting diagram revealed differences in the relationship between TT concentration and apoB among individuals with different cardiovascular disease (CVD) risk factors. Conclusions: This study elucidates a robust inverse correlation between serum TT concentration and apoB concentration, maintaining statistical significance even upon adjustment for confounding factors. These findings present a promising avenue for addressing the prevention and treatment of low testosterone and CVD.

Similarities and Differences Between Diabetes-Related and Trauma-Related Calcaneal Osteomyelitis: Comparisons Based on 681 Reported Cases.

Background: Current information were still limited regarding clinical characteristics, diagnosis, and treatment efficacy of calcaneal osteomyelitis (CO). The present study summarized similarities and differences between diabetes-related CO (DRCO) and trauma-related CO (TRCO) based on synthesis analysis of literature-reported cases. Methods: We searched the PubMed, Embase, and Cochrane Library databases to find English studies reporting DRCO and TRCO published between January 2000 and December 2021. Effective data were extracted and synthesized for comparisons. Results: Altogether 108 studies with 278 DRCO and 403 TRCO patients were analyzed. The ratio of females among the DRCO patients was significantly higher than that of the TRCO patients (37.4% vs 24.3%, P < 0.001). The median age at diagnosis of the DRCO patients was statistically older than the TRCO patients (56 vs 44 years, P < 0.001). The median symptom duration of the DRCO patients was longer than the TRCO patients (4 vs 2 months, P = 0.136), with ulcer and sinus as the top symptoms for the DRCO and TRCO patients, respectively. The positive rate of pathogen culture for the DRCO patients was significantly higher than that for the TRCO patients (94.8% vs 69.5%, P < 0.001). The DRCO patients had higher risks of infection relapse (32.3% vs 16.3%, P < 0.001) and amputation (24.8% vs 1.4%, P < 0.001), and a higher all-cause mortality (4.9% vs 1.3%, P = 0.03) than the TRCO patients. Conclusion: DRCO and TRCO shared similar and different clinical features and diagnostic issues. However, compared with TRCO, the clinical efficacy and prognosis of DRCO were worse.

Recent advances on dual inhibitors targeting HIV reverse transcriptase associated polymerase and ribonuclease H.

Reverse transcriptase (RT) plays an indispensable role in the replication of human immunodeficiency virus (HIV) through its associated polymerase and ribonuclease H (RNase H) activities during the viral RNA genome transformation into proviral DNA. Due to the fact that HIV is a highly mutagenic virus and easily resistant to single-target RT inhibitors, dual inhibitors targeting HIV RT associated polymerase and RNase H have been developed. These dual inhibitors have the advantages of increasing efficacy, reducing drug resistance, drug-drug interactions, and cytotoxicity, as well as improving patient compliance. In this review, we summarize recent advances in polymerase/RNase H dual inhibitors focusing on drug design strategies, and structure-activity relationships and share new insights into developing anti-HIV drugs.

Devascularized Bone Surface Culture: A Novel Strategy for Identifying Osteomyelitis-Related Pathogens.

The gold standard for identifying pathogens causing osteomyelitis (OM) is intraoperative tissue sampling culture (TSC). However, its positive rate remains inadequate. Here, we evaluated the efficiency of a novel strategy, known as devitalized bone surface culture (BSC), for detecting OM-related microorganisms and compared it to TSC. Between December 2021 and July 2022, patients diagnosed with OM and received both methods for bacterial identification were screened for analysis. In total, 51 cases were finally recruited for analysis. The mean age was 43.6 years, with the tibia as the top infection site. The positive rate of BSC was relatively higher than that of TSC (74.5% vs. 58.8%, p = 0.093), though no statistical difference was achieved. Both BSC and TSC detected definite pathogens in 29 patients, and their results were in accordance with each other. The most frequent microorganism identified by the BSC method was Staphylococcus aureus. Moreover, BSC took a significantly shorter median culture time than TSC (1.0 days vs. 3.0 days, p < 0.001). In summary, BSC may be superior to TSC for identifying OM-associated pathogens, with a higher detectable rate and a shorter culture time.

In Situ Constructing a Stable Solid Electrolyte Interface by Multifunctional Electrolyte Additive to Stabilize Lithium Metal Anodes for Li-S Batteries.

Lithium (Li) metal is considered to be the most promising anode due to the ultrahigh capacity and extremely low electrochemical potential. The tricky thing is that the growth of dendritic Li brings huge safety hazards to Li metal batteries. Herein, we demonstrate cerium nitrate as a multifunctional electrolyte additive to form a stable solid electrolyte interface on the metallic Li anode surface for durable Li-S batteries. The presence of Ce3+ helps to modulate the electroplating/stripping of Li and inhibits the growth of dendritic Li. An excellent cycle life exceeding 1400 h at the current density of 1 mA cm-2 can be realized in symmetric Li||Li cells. In addition, the in situ formed robust solid-electrolyte interface (SEI) layer containing cerium sulfide on the Li anode surface conduces to weaken the reducibility of Li and regulate the electrochemical dissolution/deposition reaction on the Li anode. Surprisingly, by virtue of cerium nitrate additive with a low concentration of 0.03 M, the Li-S batteries can afford a capacity of 553 mA h g-1 at 5 C and a long cycle life at 1 C with a high capacity retention of 70.4%. Therefore, this study provides a novel idea to realize a uniform and dendrite-free Li anode for practical Li-S batteries.

Analysis on Three-Dimensional Strength Influencing Factors and Control Measures of Asphalt Mixtures.

Strength is an important parameter for the design of asphalt pavement materials and structures. To study the influence of various factors on the three-dimensional strength of asphalt mixtures, three aggregate gradations (dense-graded bituminous mixture AC-13, stone mastic asphalt SMA-13 and bituminous stabilization aggregate paving mixture OGFC-13) and two binders (SBS modified bitumen and 70# base bitumen) were used to prepare the asphalt mixture specimens. Among them, SBS+SMA-13 asphalt mixture has the best performance. On this basis, the uniaxial compressive test, uniaxial tensile test and confining triaxial test were conducted on the SBS+SMA-13 asphalt mixture under six oil-stone ratios conditions (5.5%, 5.7%, 5.9%, 6.1%, 6.3%, and 6.5%), six temperatures conditions (5 °C, 10 °C, 15 °C, 20 °C, 25 °C, and 30 °C), and five loading rates conditions (1 mm/min, 2 mm/min, 3 mm/min, 4 mm/min, and 5 mm/min). In addition, a unified three-dimensional strength calculation model considering the influence of temperature, loading rate, and oil-stone ratio was proposed, and the change law of the three-dimensional strength with these above factors was revealed. Furthermore, two sets of three-factor three-level orthogonal tests were carried out on the SMA-13 asphalt mixture. The sensitivity analysis and strength regulation research between three-dimensional strength and each factor were carried out. The results show that the type of asphalt has the greatest influence on the strength of the mixture, the temperature has the second most influence, the loading rate has less influence, and the oil-stone ratio has the least influence. The strength regulations proposed to improve the strength of the asphalt mixture include the use of modified asphalt, high-temperature stability high-quality asphalt, and the lower oil-stone ratio than the Marshall optimal oil-stone ratio. The strength control measures proposed from the perspective of the three-dimensional stress state, the joint failure of each stress components and real stress states are taken into consideration.

Learning Curve for the Tension-Free Vaginal Tape-Obturator Procedure for Female Stress Urinary Incontinence: A Prospective Single-Surgeon Study.

Objective: To evaluate the learning curve in an untrained resident surgeon for the initial case series of tension-free vaginal tape-obturator (TVT-O) to treat stress urinary incontinence. Materials and Methods: A retrospective observational study was conducted in Changhai Hospital, Shanghai, China, between March 2014 and June 2018. All consecutive women included were treated by the TVT-O procedure performed by one surgeon working under the supervision of an expert surgeon. Clinical features, estimated blood loss, operative time, postoperative hospital stay, total hospital stay, adverse events, and subjective and objective cure rates were recorded. Learning curve patterns were estimated to determine the number of cases to reach a plateau using the moving average method. Results: In total, 188 patients were included for analysis. Patients ranged from 39 to 91 years, with the average age of 57.5 ± 9.7 years. The mean operative time was 32.0 minutes (range 20-60). Operative time and blood loss decreased with increase in the level of expertise, whereas postoperative hospital stay and total hospital stay were not influenced by the number of procedures performed. The number of cases required to reach a plateau was ∼30. Objective cure rate and subjective cure rate were achieved in 88.7% and 88.2% at 12 months, respectively. Groin pain was the most common postoperation complication, which continued to be present in 11.7% patients at 12 months after surgery. Conclusions: The TVT-O procedure showed encouraging objective and subjective outcomes and low complication rates, even at the initial stage of the learning curve. Thirty cases were required for a naïve resident surgeon to learn TVT-O procedures. However, long-term outcome and complications caused by the synthetic sling still need further follow-up.

Anti-diabetic activities of cis- and trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-glucopyranoside from Polygonum multiflorum.

SCOPE: Functional foods can be used alone or in combination with existing therapies in preventing and treating type 2 diabetes (T2D). Trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-glucopyranoside (trans-THSG), a dominant bioactive compound from Polygonum multiflorum (PM)-a popular medicinal food in Asia, has attracted increasing research interests due to its strong antioxidant activity. The content of naturally occurring cis-THSG (cis-2,3,5,4'-tetrahydroxystilbene 2-O-ß-glucopyranoside) was very low in PM root, but was prepared in this study by mimicking the traditional process of PM. The anti-diabetic effects of trans- and cis-THSG were evaluated in T2D to search for more efficacious food ingredient(s). METHODS AND RESULTS: Trans-THSG was chromatographically purified from PM roots and cis-THSG was prepared with our innovative process via exposure of trans-THSG to UV-light. The anti-diabetic effects of both THSGs were tested with HFD-induced male CF-1 diabetic mice. Cis-THSG was found more effective than trans-THSG in hypoglycemic effect and in ameliorating glucose intolerance and insulin resistance. In HepG2 cells, cis-THSG also demonstrated more potent activity than trans-THSG in suppressing transcription of phosphoenopyruvate carboxykinase (PEPCK). CONCLUSION: Cis-THSG can be an enriched bioactive ingredient in PM roots from post-processing and is significantly more effective against hyperglycemia than trans-THSG. One of the effective pathways was through inhibition of PEPCK.

Carcinogen 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis is accelerated in Smad3 heterozygous mice compared to Smad3 wild type mice.

Previous studies based on cell culture and xenograft animal models suggest that Smad3 has tumor suppressor function for breast cancer during early stages of tumorigenesis. In this report, we show that DMBA (7,12-dimethylbenz[a]anthracene), a chemical carcinogen, induces mammary tumor formation at a significantly higher frequency in the Smad3 heterozygous mice than in the Smad3 wild type mice. This is the first genetic evidence showing that Smad3 inhibits mammary tumor formation in a mouse model. Our findings support the notion that Smad3 has important tumor suppressor function for breast cancer.

The epigenetic effects of aspirin: the modification of histone H3 lysine 27 acetylation in the prevention of colon carcinogenesis in azoxymethane- and dextran sulfate sodium-treated CF-1 mice.

Colorectal cancer (CRC) is the third most common cancer worldwide. Chronic inflammation appears to enhance the risk of CRC. Emerging evidence has suggested that epigenetic mechanisms play an important role in CRC. Aspirin [acetylsalicylic acid (ASA)] has been shown to prevent CRC; however, the epigenetic mechanisms of its action remain unknown. This study investigated the protective role of ASA in azoxymethane (AOM)-initiated and dextran sulfate sodium (DSS)-promoted colitis-associated colon cancer (CAC) and examined the epigenetic effects, particularly on histone 3 lysine 27 acetylation (H3K27ac), underlying the preventive effect of ASA. CF-1 mice were fed with AIN-93M diet with or without 0.02% ASA from 1 week prior to AOM initiation until the mice were killed 20 weeks after AOM injection. Our results showed that AOM/DSS + ASA significantly suppressed inflammatory colitis symptoms and tumor multiplicity. AOM/DSS + ASA reduced AOM/DSS-induced protein expression and the activity of histone deacetylases (HDACs) and globally restored H3K27ac. Furthermore, AOM/DSS + ASA inhibited AOM/DSS-induced enrichment of H3K27ac in the promoters of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) that corresponded to the dramatic suppression of the messenger RNA (mRNA) and protein levels. Surprisingly, no significant changes in the H3K27ac abundance in the prostaglandin-endoperoxide synthase 2 (Cox-2) promoters or in the Cox-2 mRNA and protein expression were observed. Collectively, our results suggest that a potential novel epigenetic mechanism underlies the chemopreventive effects of ASA, and this mechanism attenuates CAC in AOM/DSS-induced CF-1 mice via the inhibition of HDACs and the modification of H3K27ac marks that suppress iNOS, TNF-α and IL-6.

Hepatoprotective Activity of Easter Lily (Lilium longiflorum Thunb.) Bulb Extracts.

The hepatoprotective activities of two different extracts, a hydroethanolic crude bulb extract (CB) and a steroidal glycoside-rich 1-butanol extract (BuOH), prepared from the bulbs of Easter lily (Lilium longiflorum Thunb.), were evaluated in a 24 week study in the female KK.Cg-A(y)/J Type 2 diabetic mouse model. Animals were divided into six groups (n = 16): control mice received Easter lily bulb extract-free drinking water together with a low- or high-fat diet (diabetic control); drinking water for the remaining groups was supplemented with CB extract (1%), BuOH extract (0.1 or 0.2%), and reference drug Metformin (0.001%), together with a high-fat diet. Both CB and BuOH extract treatment groups exhibited significantly improved liver function based on comparisons of triglycerides [diabetic 219 ± 34 mg/dL, CB 131 ± 27 mg/dL, BuOH(0.2%) 114 ± 35 mg/dL], CB total cholesterol (TC) (diabetic 196 ± 12 mg/dL, CB 159 ± 5 mg/dL), average liver mass [diabetic 2.96 ± 0.13 g, CB 2.58 ± 0.08 g, BuOH(0.1%) 2.48 ± 0.13 g], alanine transferase [diabetic 74 ± 5 units/L, CB 25 ± 1 units/L, BuOH(0.1%) 45 ± 1 units/L], and histological examinations. Glucose metabolism was improved only in CB, which was confirmed by oral glucose tolerance tests (OGTT) in diet-induced obese C57BL/6J mice exposed to CB extract. These data suggest that steroidal glycosides 1-5 might play a role in the hepatoprotective activity of the BuOH extracts, while the results of the TC measurements and OGTT study indicate that other constituents present in the CB extract are responsible for its hypocholesterolemic and hypoglycemic activity.

Ethynylphenyl carbonates and carbamates as dual-action acetylcholinesterase inhibitors and anti-inflammatory agents.

Novel ethynylphenyl carbonates and carbamates containing carbon- and silicon-based choline mimics were synthesized from their respective phenol and aniline precursors and screened for anticholinesterase and anti-inflammatory activities. All molecules were micromolar inhibitors of acetylcholinesterase (AChE), with IC50s of 28-86 µM; the carbamates were two-fold more potent than the carbonates. Two of the most potent AChE inhibitors suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation by 40%. Furthermore, these molecules have physicochemical properties in the range of other CNS drugs. These molecules have the potential to treat inflammation; they could also dually target Alzheimer's disease through restoration of cholinergic balance and inflammation suppression.

Synthesis and biological evaluation of curcumin derivatives containing NSAIDs for their anti-inflammatory activity.

Oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) was frequently associated with serious adverse effects. Inspired by curcumin-a naturally traditional Chinese medicine, a series of curcumin derivatives containing NSAIDs, used for transdermal application, were synthesized and screened for their anti-inflammatory activities in vitro and in vivo. Compared with curcumin and parent NSAID (salicylic acid and salsalate), topical application of A11 and B13 onto mouse ear edema, prior to TPA treatment markedly suppressed the expression of IL-1ß, IL-6 and TNF-α, respectively. Mechanistically, A11 and B13 blocked the phosphorylation of IκBα and suppressed the activation of p65 and IκBα. It was found that A11 and B13 may be potent anti-inflammatory agents for the treatment of inflammatory diseases.

Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages.

Nrf2 plays a critical role in defending against oxidative stress and inflammation. We previously reported that Nrf2 confers protection against ultraviolet-B (UVB)-induced inflammation, sunburn reaction, and is involved in sulforaphane-mediated photo-protective effects in the skin. In this study, we aimed to demonstrate the protective role of Nrf2 against inflammation-mediated extracellular matrix (ECM) damage induced by UVB irradiation. Ear biopsy weights were significantly increased in both Nrf2 wild-type (Nrf2 WT) and knockout (Nrf2 KO) mice one week after UVB irradiation. However, these weights increased more significantly in KO mice compared to WT mice, suggesting a greater inflammatory response in KO mice. In addition, we analyzed the protein expression of numerous markers, including macrophage inflammatory protein-2 (MIP-2), pro-matrix metalloproteinase-9 (MMP-9), and p53. p53, a regulator of DNA repair, was overexpressed in Nrf2 KO mice, indicating that the absence of Nrf2 led to more sustained DNA damage. There was also more substantial ECM degradation and increased inflammation in UVB-irradiated Nrf2 KO mice compared to UVB-irradiated WT mice. Furthermore, the protective effects of Nrf2 in response to UVB irradiation were mediated by increased HO-1 protein expression. Collectively, our results show that Nrf2 plays a key role in protecting against UVB irradiation and that the photo-protective effect of Nrf2 is closely related to the inhibition of ECM degradation and inflammation.

Genome-wide analysis of DNA methylation in UVB- and DMBA/TPA-induced mouse skin cancer models.

AIMS: Ultraviolet irradiation and carcinogens have been reported to induce epigenetic alterations, which potentially contribute to the development of skin cancer. We aimed to study the genome-wide DNA methylation profiles of skin cancers induced by ultraviolet B (UVB) irradiation and 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-1,3-acetate (TPA). MAIN METHODS: Methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing was utilized to ascertain the DNA methylation profiles in the following common mouse skin cancer models: SKH-1 mice treated with UVB irradiation and CD-1 mice treated with DMBA/TPA. Ingenuity® Pathway Analysis (IPA) software was utilized to analyze the data and to identify gene interactions among the different pathways. KEY FINDINGS: 6003 genes in the UVB group and 5424 genes in the DMBA/TPA group exhibited a greater than 2-fold change in CpG methylation as mapped by the IPA software. The top canonical pathways identified by IPA after the two treatments were ranked were pathways related to cancer development, cAMP-mediated signaling, G protein-coupled receptor signaling and PTEN signaling associated with UVB treatment, whereas protein kinase A signaling and xenobiotic metabolism signaling were associated with DMBA/TPA treatment. In addition, the mapped IL-6-related inflammatory pathways displayed alterations in the methylation profiles of inflammation-related genes linked to UVB treatment. SIGNIFICANCE: Genes with altered methylation were ranked in the UVB and DMBA/TPA models, and the molecular interaction networks of those genes were identified by the IPA software. The genome-wide DNA methylation profiles of skin cancers induced by UV irradiation or by DMBA/TPA will be useful for future studies on epigenetic gene regulation in skin carcinogenesis.

[Biological characteristics of PHA-induced CIK cells and its killing activity to K562 cells].

The purpose of study was to investigate the in vitro proliferation ability of PHA-induced CIK cells and traditionally prepared CIK cells, the effector cell level and its influence on killing activity to K562 cells, and to analyze the difference between them. The peripheral blood mononuclear cells(PBMNC) of healthy persons were isolated and divided into A and B group. The CIK cells in A group were obtained by using traditional culture method, the CIK cells in B group were prepared by PHA induction. During the cultivation, the cell survival rate and cell absolute value in the cell culture system were counted every 3 days. On day 15 of culture, the cell immunophenotype of 2 groups were detected by flow cytometry, and the ratios of CD3(+)CD56(+), CD3(+)CD8(+) and CD3(+)CD4(+) cells in total cell amount of culture system were accounted. Meantime, the killing activity to K562 cells in different effector-target ratios was detected by using CCK-8 kit between the 2 groups. The results showed that the method of preparing CIK by PHA induction promoted the cell proliferation more than that of the traditional method (P < 0.05), moreover, both the survival rate of cells in 2 groups was more than 90%. The CD3(+)CD8(+), CD3(+)CD56(+) cell ratio in 2 groups obviously increased. As compared with traditional method, the CD3(+)CD8(+) cell level in B group was enhanced (P < 0.05); but there were no statistical differences in increase of CD3(+)CD56(+) cell level and decrease of CD3(+)CD4(+) cell level between 2 groups. while the effector-target ratio is 5:1, 10:1, 20:1 and 40:1, the killing activity of PHA-induced CIK cells to K562 cells was more stronger than traditionally-prepared CIK cells (P < 0.05), moreover, along with increase of effector-target ratio, the difference of killing activity to K562 cells in 2 groups significantly increased. It is concluded that compared with traditional method for preparing CIK cells, the new way by PHA induction can increase the proliferation of CIK cells obviously, enhance the ratio of CD3(+)CD8(+) cells and strengthen the killing activity to the K562 cells. This new way provides a new source of CIK cells and reliable evidence for cyto-immune therapy of leukemia and other tumors.

In vitro and in vivo anti-inflammatory effects of a novel 4,6-bis ((E)-4-hydroxy-3-methoxystyryl)-1-phenethylpyrimidine-2(1H)-thione.

Inflammation plays a critical defensive role in the human body. However, uncontrolled or aberrant inflammatory responses contribute to various acute and chronic diseases. The Nrf2-ARE pathway plays a pivotal role in the regulation of inflammatory markers, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). On the basis of this concept, we synthesized a novel anti-inflammatory 4,6-bis ((E)-4-hydroxy-3-methoxystyryl)-1-phenethylpyrimidine-2(1H)-thione (HPT), and in vitro experiments using HepG2-C8 ARE-luciferase-transfected cells demonstrated the induction of Nrf2-ARE activity. In lipopolysaccharide (LPS)-induced RAW 264.7 cells, HPT treatment reduced the production of nitric oxide (NO) as well as the protein and mRNA expression levels of COX-2 and iNOS, in a dose-dependent manner. In addition, HPT suppressed the mRNA expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6. In LPS-induced macrophages, HPT inhibited COX-2 and iNOS by blocking the activation of p38 and c-Jun NH2-terminal kinase (JNK) but not extracellular signal-regulated kinase (ERK1/2). Furthermore, an in vivo anti-inflammatory study was performed using a TPA-induced skin inflammation mouse model, and the results showed that HPT reduced TPA-induced inflammation and attenuated the expression of COX-2 and iNOS in TPA-induced mouse skin tissue. Thus, HPT demonstrated anti-inflammatory activity both in LPS-induced RAW 264.7 cells and TPA-stimulated mouse skin and may therefore serve as a potential anti-inflammatory agent.

Inhibition of IL-6 expression in LNCaP prostate cancer cells by a combination of atorvastatin and celecoxib.

In the present study, we investigated the effect of a combination of atorvastatin and celecoxib on the formation of interleukin (IL)-6, a cytokine that is increased during the progression of LNCaP tumors from androgen dependence to androgen independence. Culturing LNCaP cells in androgen­depleted (AD) medium increased the levels of IL-6 and survivin, and treatment of the cells in AD medium with a combination of atorvastatin and celecoxib strongly inhibited the increase in IL-6 and survivin which is one of the downstream targets of the IL-6 signaling pathway. Addition of recombinant IL-6 partially abrogated the combined effect of atorvastatin and celecoxib on apoptosis in LNCaP cells cultured in AD medium. In SCID mice, we found that the levels of IL-6 and survivin expression were increased when LNCaP tumors became androgen-independent. Treatment of the mice with atorvastatin or celecoxib alone caused decrease in the levels of IL-6 and survivin as LNCaP tumors became androgen-independent, but treatment of the mice with a combination of celecoxib and atorvastatin resulted in a much stronger inhibition in the increase in IL-6 and survivin expression. Our results indicate that decreases in IL-6 and survivin levels by atorvastatin and celecoxib administration are associated with increased apoptosis in LNCaP cells treated with this drug combination. Our in vivo studies indicate that the inhibitory effect of a combination of atorvastatin and celecoxib on the progression of androgen-dependent LNCaP xenograft tumors to androgen independence is associated with inhibition of the increase in IL-6 and survivin that occurs when androgen-dependent LNCaP prostate tumors become androgen-independent.

Anti-proliferative, anti-inflammatory and antioxidant effects of curcumin analogue A2.

In the present study, we determined the anti-proliferative, anti-inflammatory and antioxidant effects of a curcumin analogue, 2,6-bis(3,4-dihydroxybenzylidene) cyclohexanone (designated as A2). In vitro studies showed that A2 had a stronger inhibitory effect on the growth of mouse macrophage RAW 264.7 cells than curcumin. A2 also showed a stronger inhibitory effect than curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in NF-κB activation and IL-1ß expression as well as in aldose reductase activity. A2 was a stronger antioxidant than curcumin as determined by inhibition of lipid peroxidation, inhibition of 1,1-diphenyl-2-picryl-hydrazyl free radical formation, and inhibition of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical formation. In vivo studies indicated that A2 was more potent than curcumin for inhibiting TPA-induced ear edema and TPA-induced increases in IL-1ß. In addition, oral administration of A2 at a dose of 2,000 mg/kg body weight did not cause acute toxicity in mice. Taken together, the results of our study indicate that the curcumin analogue A2 has stronger anti-proliferative, anti-inflammatory and antioxidant activities than curcumin.

Primary alveolar echinococcosis (Echinococcus multilocularis) of the adrenal gland: report of two cases.

We retrospectively analyzed two rare cases of primary alveolar echinococcosis of the adrenal gland that were misdiagnosed. One male patient was asymptomatic and the lesion was found incidentally, and the other female patient had an obscure abdominal pain. No masses were found in the epigastric region of either patient. Computed tomography (CT) scans revealed oval masses with indistinct margins adjacent to organs. The lesions were slightly enhanced by contrast medium, showing cystic and solid components with a cobbled road appearance. Both cases were diagnosed as adrenal malignant tumors, and adrenalectomies were performed. Postoperative pathology reports confirmed adrenal alveolar echinococcosis. Neither patient had recurrence at 2 years of follow-up. The cobbled road appearance of this disease on CT images may represent the early-stage image of alveolar echinococcosis.