Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

Tunica vaginalis testis metastasis as the first clinical manifestation of pancreatic adenocarcinoma:A case report

BACKGROUND Metastases from pancreas or ampullary malignancies are common,but the spread to testicle and paratesticular tissue is exceedingly rare.To the best of our knowledge,fewer than 30 cases have been reported in the literature.More rarely,metastasis to tunica vaginalis testis occurs without involvement of the testes and epididymis.CASE SUMMARY A 65-year-old male who complained of painless swelling of the left scrotum for over 1 wk was referred to the Department of Urology.Scrotal ultrasound showed left testicular hydrocele with paratesticular masses.Chest computed tomography revealed lung metastasis and enlarged left supraclavicular lymph node.The blood tumor markersalpha-fetoprotein,human chorionic gonadotropin,and serum lactate dehydrogenase were withinnormal limits.The preoperative diagnosis was left testicular tumor with lung metastasis.Then radical orchidectomy of the left testicle and high ligation of the spermatic cord were performed,and postoperative histopathology suggested metastatic tumors that was confirmed by an abdominal computed tomographic scan.The positive computed tomography findings,in conjunction with the expression of cytokeratin 7(CK7),CK20,CK5/6,and absence of expression of Wilms’tumor suppressor gene 1,calretinin,melanocyte,prostate-specific antigen,thyroid transcription factor-1,GATA binding protein 3,caudal type homeobox 2,and napsinA supported the diagnosis of pancreatic adenocarcinoma.The outcome of this patient was unsatisfactory,and he died 3 mo later.CONCLUSION This case suggests that pancreatic metastatic carcinoma must be considered in the differential diagnosis of scrotal enlargement.The advanced age of the patient wassuggestive of a secondary testicular tumor.In addition,careful physical examination and ultrasonography as well as radiological examination have become a standard modality.

Solitary fibrous tumor of the renal pelvis:A case report

BACKGROUND Solitary fibrous tumor(SFT)is a rare mesenchymal neoplasm.SFT derived from the renal pelvis is an exceedingly rare entity.In this study,we report a case of renal pelvis SFT and review the relevant literature on this rare tumor.CASE SUMMARY A 76-year-old man was hospitalized due to right lumbar and abdominal pain.Abdominal computed tomography showed a hypervascular space-occupying renal lesion,sized 2.3 cm×1.8 cm.Based on the computed tomography findings,the patient was diagnosed with right renal pelvis tumor and underwent nephrectomy.Postoperative immunohistochemical results confirmed the diagnosis.As of the 3-year follow-up,there were no signs of recurrence,and the patient has recovered well.CONCLUSION We report a rare case of SFT derived from the renal pelvis and discuss the imaging and histopathological features that distinguish renal pelvis SFT from other renal pelvis tumors.

Fabrication, Crosslinking and in vitro Biocompatibility of a Novel Degradable Nano-structure Urethral Tubular Scaffold

A degradable poly（lactic-co-glycolic acid, LA：GA=80：20）（PLGA） urethral tubular scaffold was fabricated by electrospinning. In order to enhance the mechanical properties, the scaffold was crosslinked with glutaraldehyde. The structure and properties of the crosslinked scaffolds were investigated by the mechanical property testing, scanning electron microscopy（SEM）, degradability test in vitro and 3-（4,5）-dimethylthiahiazo（-z-yl）-3,5-diphenytetrazo- liumromide（MTT）. The results show that the scaffold has the nano-structure. The pore size and the porosity are suitable for cell seeding, growth and extracellular matrix production. Although influenced by the crosslinking slightly, the pore size and the porosity could still support cell proliferation and tissuse formation. The mechanical properties are remarkably increased by the crosslinking of glutaraldehyde, and it could meet the demands of a urethral stent. The scaffold could completely collapse within 70 d. The results of the biocompatibility test show that the PLGA scaffold had no cytotoxicity.

Current status of diagnosis and treatment of bladder cancer in China-Analyses of Chinese Bladder Cancer Consortium database

Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.

Photoswitchable semiconducting polymer dots with photosensitizer molecule and photochromic molecule loading for photodynamic cancer therapy

Photodynamic therapy(PDT)is a new and rapidly developing treatment modality for dinical cancer therapy.Semiconductor polymer dots(Pdots)doped with photosensitizers have been successfully applied to PDT,and have made progress in the field of tumor therapy.However,the problems of severe photosensitivity and limited tisue penetration depth are needed to be solved during the implementation process of PDT.Here we developed the Pdots doped with photosensitizer molecule Chlorin e6(Ce6)and photochromic molecule 1,2-bis(2,4-dimethy1-5 phenyl-3-thiophene)-3,3,4,5-hexafuoro-1-cyclopentene(BTE)to construct a photoswitchable nanoplatform for PDT.The Ce6-BTE-doped Pdots were in the green region,and the tissue penetration depth was increased compared with most Pdots in the blue region.The reversible conversion of BTE under different light irradiation was utilized to regulate the photodynamic effect and solve the problem of photosensitivity.The prepared Ce6-BTE-doped Pdots had small size,excellent optical property,efficient ROS generation and good photoswitchable ability.The cellular uptake,cytotoxicity,and photodynamic effect of the Pdots were detected in human colon tumor cells.The experiments in vitro indicated that Ce6-BTE-doped Pdots could exert excellent photodynamic effect in ON state and reduce photosensitivity in OFF state.These results demonstrated that this nanoplatform holds the potential to be used in clinical PDT.

Clopidogrel delays and can reverse diabetic nephropathy pathogenesis in type 2 diabetic db/db mice

BACKGROUND Diabetic nephropathy(DN)is the principal cause of end-stage renal disease.Previous studies have shown that clopidogrel can prevent the early progression of renal injury.AIM To elucidate whether clopidogrel is beneficial against DN by using a db/db mouse model.METHODS db/db mice with a higher urinary albumin/creatinine ratio(ACR)relative to ageand sex-matched wild-type control mice were randomly allocated to clopidogrel and vehicle treatment groups.Clopidogrel was administered at doses of 5,10,and 20 mg/kg by gavage for 12 wk.Body mass,blood glucose level,and urinary creatinine and albumin concentrations in each group were measured before and after the intervention.Renal fibrosis was evaluated using periodic acid-Schiff and Masson’s trichrome staining.The renal protein expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and F4/80 was assessed using immunohistochemistry.Urinary TNF-α,monocyte chemoattractant protein-1(MCP-1),and IL-6 levels were analyzed using enzyme-linked immunosorbent assay;TNF-αand IL-1βmRNA expression was measured using real-time quantitative polymerase chain reaction.The protein expression of fibronectin(FN)and collagen I was assessed using immunohistochemistry.RESULTS Clopidogrel treatment did not affect the body mass or blood glucose level of the db/db mice;however,it increased bleeding time and reduced urinary ACR in a dose-dependent manner.Immunohistochemical staining revealed an amelioration of renal fibrosis,significantly lower deposition of FN and collagen I,and significantly lower expression of the proinflammatory cytokines TNF-αand IL-1βand lower levels of urinary TNF-αand MCP-1 in the clopidogrel-treated db/db mice(P<0.05).Furthermore,clopidogrel significantly reduced macrophage infiltration into the glomeruli of the db/db mice.CONCLUSION Clopidogrel significantly reduced renal collagen deposition and fibrosis and prevented renal dysfunction in db/db mice,most likely through inhibition of renal macrophage infiltration and the associated inflammation.

Identification of MSA-2: An oral antitumor non-nucleotide STING agonist

In a recent study in Science,Pan et al.1 identified an orally available non-nucleotide human stimulator of interferon genes(STING)agonist,MSA-2(benzothiophene oxobutanoic acid),with excellent safety tolerance in vivo.The noncovalently tethered dimers of MSA-2 could bind STING with nanomolar affinity,and the acidic tumor microenvironment would substantially increase the cell entry and retention of MSA-2 and its dimerized interaction with STING,thus leading to a superior antitumor potency of combined MSA-2 and anti-PD-1 treatments.This work has encouraged further design and discovery of clinical human STING agonists for systematic cancer therapy(Fig.1).

Crosslinked Polystyrene Beads Modified with Sulfonyl Groups and Their Application in Aromatic/Aliphatic Hydrocarbons Separation

The separation of aromatic hydrocarbons from aromatic/aliphatic mixtures was investigated with cross- linked polystyrene（CPS） beads modified with sulfonyl groups. Three sulfonating agents, i.e. benzenesulfonyl chlo- ride（BsCl）, 4-toluene sulfonyl chloride（TsC1） and methanesulfonyl chloride（MsC1） were used to prepare sulfonyl CPS beads by Friedel-Crafts reaction. The CPS beads modified with BsC1 exhibited higher sulfonation rate than those modified with MsC1 and TsCI and obtained optimum selectivity in the experiments of toluene/n-heptane separation. Further separation tests with various other aromatic/aliphatic mixtures were carried out at an initial aromatic concen- tration of 13%（mass fraction） with the results showing that the modified beads have preferential selectivity for aro- matic hydrocarbons in all aromatic/aliphatic mixtures, and especially a separation factor of 8.21 and a swelling ratio of 30% for toluene/cyclohexane system. The thermal stability and regeneration test indicate that the used polystyrene beads can be recovered through heat-drying and reused effectively.

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo

Objective:To explore the influences of andrographolide(Andro)on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.Methods:For in vitro experiments,T24 cells were stimulated with Andro(0-40μmol/L)and 5637 cells were stimulated with Andro(0 to 80μmol/L).Cell growth,migration,and infiltration were assessed using cel counting kit-8,colony formation,wound healing,and transwel assays.Apoptosis rate was examined using flow cytometry.In in vivo study,the antitumor effect of Andro(10 mg/kg)was evaluated by 5637 tumor-bearing mice,and levels of nuclear factorκB(NF-κB)and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.Results:Andro suppressed growth,migration,and infiltraion of bladder cancer cells(P 0.05or P 0.01).Additionally,Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines.Furthermore,Andro inhibited bladder cancer growth in mice(P 0.01).The expression of p65,p-AKT were suppressed by Andro treatment in vitro and in vivo(P 0.05 or P 0.01).Conclusions:Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cel s by interfering with NF-κB and PI3K/AKT signaling in vitro and in vivo.

Recurrent paratesticular dedifferentiated iposarcoma after contralateral radical orchiectomy

Dear Editor, The concept of dedifferentiated liposarcoma （DDL） was first proposed by Evans in 1979.1 Liposarcomas, including DDL and well-differentiated liposarcoma （WDL）, occur most frequently in 50- to 70-year-old men within the retroperitoneum or extremities. DDL has a propensity for local recurrence, but distant metastasis is rare. Retroperitoneal DDL has a significantly worse prognosis than disease at other locations.2 As paratesticular DDL is a rare entity, clinicians need to differentiate it from other common scrotal neoplasms or swelling diseases.