The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia

Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management.

Medical therapy for clinical benign prostatic hyperplasia:α1 Antagonists,5α reductase inhibitors and their combination

Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting.

Relation between Baseline Lipid Levels and Effectiveness of HMG-CoA Reductase Inhibitors in Patients with Hyperlipidemia

Objective To evaluate whether the effects of HMG - CoA reductase inhibitors on patients with hyperlipidemia are closely related to baseline lipid levels. Methods The data analyzed originated from 3 separate multicenter clinical trials with similar designs during 1994 to 1999. 166 patients with mean age 58. 9±9. 2 years were involved in Simvastatin Clinical Trial with simvastatin 10 mg once daily for 8 weeks. 146 patients with mean age 57. 9±8. 7years were involved in Lovastatin Clinical Trial with lovastatin 20 mg once daily for 8 weeks. 105 patients with mean age 57. 8±9. 3 years were involved in Atorvastatin Clinical Trial with atorvastatin 10 mg once daily for 6 weeks. Baseline total cholesterol (TC) was more than 5. 98 mmol. L - 1, and baseline triglyceride (TG) was less than 4. 52 mmo. L - 1. The patients were grouped by baseline lipid levels. Results The higher the baseline TC, low density lipoprotein cholesterol (LDL - C) and TG levels were, the more effective the simvastatin, lovastatin, or atorvastatin was in reducing serum TC, LDL - C, and TG, respectively. A positive linear correlation was found between baseline values and effects of simvastatin, lovastatin, or atorvastatin in reducing serum TC, LDL - C, and TG, respectively. Conclusion The changes of reduction on serum lipid with HMG - CoA reductase inhibitors in patients with hyperlipidemia were influenced by baseline lipid levels.

Long-term effects of various types of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on changes in glomerular filtration rate in Korea

Few long-term follow-up studies have compared the changes in renal function according to the type of statin used in Korea.We compared the long-term effects of statin intensity and type on the changes in the glomerular filtration rate(GFR).We extracted data of patients who took statin for the first time.We analyzed whether or not different statins affect the changes in GFR at 3 months after baseline and 4 years after.We included 3678 patients and analyzed the changes in GFR.The GFR decreased by 3.2%±0.4%on average 4 years after the first statin prescription,indicating statistically significant deterioration(from 83.5±0.4 mL/min/1.73 m2 to 79.9±0.4 mL/min/1.73 m2,P<0.001).When comparing the GFR among different statins,significant differences were observed between atorvastatin and fluvastatin(−5.3%±0.7%vs.1.2%±2.2%,P<0.05)and between atorvastatin and simvastatin(−5.3%±0.7%vs.−0.7%±0.8%,P<0.05).In pitavastatin(odds ratio[OR]=0.64,95%confidence interval[CI]=0.46-0.87,P<0.005)and simvastatin(OR=0.69,95%CI=0.53-0.91,P<0.008),the GFR rate that decreased by<60 mL/min/1.73 m2 was significantly lower than that of atorvastatin.Regarding long-term statin intake,GFR changed with the type of statin.This work is the first in Korea to compare each statin in terms of changes in the GFR after the statin prescription.

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

BACKGROUND Ribonucleotide reductase(RR)is a key enzyme in tumor proliferation,especially its subunit-RRM2.Although there are multiple therapeutics for tumors,they all have certain limitations.Given their advantages,traditional Chinese medicine(TCM)monomers have become an important source of anti-tumor drugs.Therefore,screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development.AIM To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2.METHODS The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients.TCM monomers that potentially act on RRM2 were screened via literature mining.Using AutoDock software,the screened monomers were docked with the RRM2 protein.RESULTS The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues,and it was negatively correlated with the overall survival rate of patients with the majority of tumor types.Through literature mining,we discovered that berberine,ursolic acid,gambogic acid,cinobufagin,quercetin,daphnetin,and osalmide have inhibitory effects on RRM2.The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein,which mainly interacted through hydrogen bonds and hydrophobic force.The main binding sites were Arg330,Tyr323,Ser263,and Met350.CONCLUSION RRM2 is an important tumor therapeutic target.The TCM monomers screened have a good binding capacity with the RRM2 protein.

Aldo-keto reductases:Role in cancer development and theranostics

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various cancers.AKRs are aberrantly expressed in a wide range of malignant tumors.Dysregulated expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to chemoresistance.AKRs have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and progression.Inhibition of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for cancer.Several classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical trials.Many AKR inhibitors from natural sources also exhibit anticancer effects.Small molecule inhibitors targeting specific AKR isoforms have shown promise in preclinical studies.These inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to chemotherapy.In this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug resistance.Finally,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

Differential expression of 5-alpha reductase sozymes in the prostate and its clinical implications

The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone （T） and dihydrotestosterone （DHT）. T is converted to DHT by 5-alpha reductase （5-AR） isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors （5-ARI） are commonly used for the treatment of benign prostatic hyperplasia （BPH） and were once promoted as chemopreventive agents for prostate cancer （PCa）. This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.

Inhibitory effect of fluvastatin on ileal ulcer formation in rats induced by nonsteroidal antiinflammatory drug

AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs)cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors on the ulceration in small intestines of rats.METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method.RESULTS: Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin)did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others(pravastatin, atorvastatin).CONCLUSION: Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.

INHIBITORY EFFECT OF FLUVASTATIN ON AORTIC INTIMAL THICKENING IN NORMOCHOLESTEROLEMIC RABBITS

The anti atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods.Fifty six rabbits were randomly divided into eight groups(n=7,each).Fluvastatin was given mixed with food at daily dose of8mg/kg starting 5 days before catheterization.Light microscope,immunohistochemistry,transmission electron microscope and RT PCR assay were applied to assess vascular smooth muscle cell (VSMC)proliferation and apoptosis, as well as oncogene expression in vascular wall. Results.At day 10 and day 15 after catheter induced denudation intima/media(I/M)thickness ratio was obviously higher, and also the percentage of PCNA positive cells and TUNEL positive cells in media was significantly higher compared with controls.The intimal hyperplasia was mostly composed of α SM actin positive cells.In rabbits given fluvastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvastatin.The overexpression of proto oncogene H ras mRNA and decreased expression of anti oncogene p53 mRNA were found after vascular injury,whereas fluvastatin significantly reduced H ras mRNA and increased p53 mRNA expression. Conclusion.Proliferation of VSMC in the media and the migration to the intima can be inhibited,and apoptosis of VSMC be induced by short term use of fluvastatin after balloon catheter denudation,independent of serum lipid change.The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.

Effects of Pravastatin on neuroprotection and neurogenesis after cerebral ischemia in rats

Objective Statins inhibit hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase activity and lower total serum cholesterol levels. We investigated the effects of Pravastatin on neuroprotection and neurogenesis in the dentate gyrus （DG）, subventricular zone （SVZ） and striatum after cerebral ischemia in rats. Methods The filament method was used for temporary middle cerebral artery occlusion （tMCAO）. Pravastatin or saline post-ischemically were administered at subsequent time points： 6 h after tMCAO, and then on every subsequent day up to day 14 after tMCAO. Neurological outcome was investigated by using a neuroscore, the beam balance test and the rotarod test. Cholesterol and triglycerides levels were determined by blood sample analysis prior to sacrifice. Infarct area was calculated by microtubule-associated protein 2 （MAP2） staining. Neurogenesis was evaluated by triple staining with bromodeoxyuridine （BrdU）, doublecortin （DCX）, and neuronal nuclei （NeuN）. Results Compared with the control groups, Pravastatin treated animals were significantly improved in neurological outcome in rotarod test, with smaller infarct size. Pravastatin increased BrdU- positive cells number in the DG （P = 0.0029） and the SVZ （P = 0.0280） but not in the striatum （P = 0.3929）. Furthermore, Pravastatin increased BrdU-labeled DCX positive cells number in the DG （P = 0.0031）, SVZ （P = 0.0316） and striatum （P = 0.0073）. We also observed a DCX-positive cells stream from the SVZ to the striatum, suggesting a migration route of those immature neurons. No significant differences of total serum cholesterol and triglycerides were observed between groups. Conclusion The Pravastatin administration strategy is safe and could promote neurological recovery in ischemic stroke. Pravastatin induces neurogenesis in the DG and SVZ, and increases the number of migration cells in the striatum. These effects are independent of the cholesterol-lowering property of Pravastatin.

Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway

Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.

Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials

OBJECTIVE： To evaluate the efficacy of α-lipoic acid（ALA） plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy（DPN）. DATA SOURCES： The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were（diabetic peripheral neuropathy or diabetic neuropathy or DPN） AND（α-lipoic acid or lipoic acid or thioctic acid） AND epalrestat. DATA SELECTION： All of the eligible studies met the following inclusion criteria：（1） Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.（2） The minimum duration of treatment was 2 weeks.（3） The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.（4） Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES： The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity（MNCV）, median sensory nerve conduction velocity（SNCV）, peroneal MNCV and peroneal SNCV.RESULTS： Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies（RR = 1.29, 95% CI： 1.21–1.38; RR = 1.43, 95% CI： 1.34–1.54, respectively）. ALA plus epalrestat combination therapy also significantly improved median MNCV（WMD = 5.41, 95% CI： 2.07–8.75）, median SNCV（WMD = 5.87, 95% CI： 1.52–10.22）, peroneal MNCV（WMD = 5.59, 95% CI： 2.70–8.47） and peroneal SNCV（WMD = 4.57, 95% CI： 2.46–6.68）.CONCLUSION： ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.

Statins and the risk of colorectal cancer: An updated systematic review and meta-analysis of 40 studies

AIM: To investigate the association between statin use and colorectal cancer risk, we conducted an updated meta-analysis of published studies.

Do statins reduce hepatitis C RNA titers during routine clinical use?

AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).METHODS: Medical records were reviewed for 6463 patients with documented HCV infection at a single center between March 2004 and September 2006. Patients with confi rmed viremia and meeting inclusion criteria were assigned to one of three groups: Group A (n = 50), dyslipidemic patients with statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group B (n = 49), dyslipidemic patients with prior or future statin usage but not at the time of HCV RNA PCR determination; and Group C (n = 102), patients without statin usage during the study period. The primary analysis explored the effect of statin therapy on HCV viremia. Secondary analyses assessed class effect, dose response, and effect of other lipid-lowering therapies on HCV viral titers.RESULTS: Median HCV RNA titers did not signif icantly differ among the three groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000 IU/mL).For those subjects with longitudinal assessment of HCV viremia prior to and while on statins, there were no signif icant differences between pre- and post-HCV viral titers. Additionally, no differences in HCV titers were observed at any dose level of the most prescribed statin, simvastatin. However, hypertriglyceridemia independently correlated with HCV titers, and niacin exposure was associated with signif icantly lower viral titers (P < 0.05).CONCLUSION: There was no apparent effect of statins on HCV viral replication in this analysis. Further investigation is warranted to explore the possible antiviral properties of triglyceride-lowering agents and their potential role as adjuncts to standard HCV therapy.

Effectiveness of statins vs.exercise on reducing postprandial hypertriglyceridemia in dyslipidemic population:A systematic review and network meta-analysis

Background:Individuals at risk of suffering cardiovascular disease(CVD) present with larger increases in blood trigyceride(TG) concentration after a high-fat meal than do healthy individuals.These postprandial hypertriglyceride levels are an independent risk factor for CVD.Prescription of statins and a bout of prolonged exercise are both effective in lowering postprandial hypertriglyceride levels.We aimed to evaluate the comparative effectiveness of statins vs.a bout of aerobic exercise in reducing fasting and postprandial TG(PPTG) concentrations in indiv、duals at high nsk of developing CVD.Methods:Thirty-seven sltudies from a systematic literature search of the PubMed,EMBASE,and Cochrane databases were included in this review.The selected studies conducted trials involving statin therapy(n=20) or a bout of aerobic exercise(n=19) and measured their impact on PPTG levels as the outcome.Two studies analyzed both treatments and were included in duplicate.The meta-analysis was constructed using a random-effects model to calculate the mean difference(MD).The Student t test was used to compare the data sets for statins vs.exercise.Results:Overall,statin and exercise interventions showed similar reductions in PPTG levels,with an MD of-0.65 mmol/L for statins(95% confidence interval(95%CI):-0.54 to-0.77;p <0.001) and-0.46 mmol/L for exercise(95%CI:-0.21 to-0.71;p <0.01).However,statins lowered fasting TG levels more than exercise(MD=-1.54 mmol/L,95%CI:-2.25 to-0.83;p=0.009).Conclusion:Although aerobic exercise is effective in lowering blood TG levels,statins seem to be more efficient,especially in the fasted state.A combination of exercise and statins might reveal a valuable approach to the treatment and prevention of CVD.More studies are required to determine the underlying mechanisms and the possible additive effects of these interventions.

Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data

BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus(T2DM).Statin and metformin are commonly used medications in T2DM patients,and some studies showed statin-or metformin-induced neuropathy.AIM To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies.METHODS Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used.Patients with T2DM and no complications were divided into statin/metformin/statin+metformin users and non-users.Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems,10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants.Logistic regression analyses were conducted to examine the associations between statin/metformin/statin+metformin therapies and the incidence of neuropathy.Propensity score(PS)matching was performed on the basis of age,sex and comorbidities.RESULTS Overall,34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017,respectively.Statin therapy was associated with increased risks of neuropathy in 2016 and 2017[PS-matched odds ratio(OR)=1.22,95%confidence interval(CI):1.08-1.38;PS-matched OR=1.17,95%CI:1.03-1.33,respectively].Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017(PS-matched OR=0.30,95%CI:0.21-0.42;PSmatched OR=0.44,95%CI:0.32-0.60,respectively).Combined statin+metformin therapy was not significantly associated with neuropathy in 2016 or 2017(PSmatched OR=0.85,95%CI:0.61-1.19;PS-matched OR=0.95,95%CI:0.66-1.38,respectively).CONCLUSION Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM,but metformin therapy showed the opposite association.

Statins and Breast Cancer: An Overview of the Current Situation

Statins [(3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG-CoA reductase, abbreviated HMGCR) inhibitors] inhibit cholesterol synthesis and are commonly used in the treatment and prevention of cardiovascular diseases. Preclinical and clinical studies have shown that the drug can be effective in several cancers including breast cancer which is the second most frequent cancer in the world and the commonest one among women. In breast cancer cell lines statins reduce proliferation, increase apoptosis, decrease invasion and sensitize them to radiation. Clinical trials in breast cancer patients have shown positive outcome in terms of decreased recurrence rate, decreased mortality and positive role as neoadjuvant agent. They may have a particular role in treatment-resistant cases like triple-negative or inflammatory breast cancer which have a poorer prognosis. There is also evidence of their potential use in metastatic bone disease from breast cancer. When statins inhibit 3-hydroxy-3-methylgutaryl CoA reductase which is the rate-limiting enzyme of the mevalonate pathway, the levels of mevalonate as well as its downstream products are decreased. Hence cancer growth is inhibited by reduced prenylation of CAAX proteins, N-Glycosylation of growth factor receptors and synthesis of membrane and steroid among others. Also statins are relatively cheap and can contribute to decrease the high cost of cancer treatment. However studies till now have not shown any association with decreased breast cancer incidence. In addition there are doubts regarding safety of statins when used over a prolonged period of time. Although statins are relatively safe with myotoxicity and hepatotoxicity being their major side effects, evidence regarding issues like drug interactions with anti-cancer drugs is lacking.

Statin as a therapeutic agent in gastroenterological cancer

Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase,the rate-limiting enzyme of the mevalonate pathway,and are widely used as an effective and safe approach handle hypercholesterolemia.The mevalonate pathway is a vital metabolic pathway that uses acetyl-CoA to generate isoprenoids and sterols that are crucial to tumor growth and progression.Multiple studies have indicated that statins improve patient prognosis in various carcinomas.Basic research on the mechanisms underlying the antitumor effects of statins is underway.The development of new anti-cancer drugs is progressing,but increasing medical costs from drug development have become a major obstacle.Readily available,inexpensive and well-tolerated drugs like statins have not yet been successfully repurposed for cancer treatment.Identifying the cancer patients that may benefit from statins is key to improved patient treatment.This review summarizes recent advances in statin research in cancer and suggests important considerations for the clinical use of statins to improve outcomes for cancer patients.

Research progress of Statins

Statins are one of the most popular lipid-lowering drugs( LLDs). Upon oral administration,these drugs are well absorbed by the intestine and effectively used for the treatment of dyslipidemias. This manuscript aims to investigate the demographics of the data who used Statins,review the benefits and challenges of Statins and the future of the treatment.

Search of inhibitors of aldose reductase for treatment of diabetic cataracts using machine learning

Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of the human eye that causes cataracts is managed by the Aldose Reductase Enzyme(AR),and it is been found that AR inhibitors may mitigate the onset of diabetic cataracts.There exists a large pool of natural and synthetic AR inhibitors that can prevent diabetic complications,and the development of a machine-learning(ML)prediction model may bring new AR inhibitors with better characteristics into clinical use.Methods:Using known AR inhibitors and their chemical-physical descriptors we created the ML model for prediction of new AR inhibitors.The predicted inhibitors were tested by computational docking to the binding site of AR.Results:Using cross-validation in order to find the most accurate ML model,we ended with final cross-validation accuracy of 90%.Computational docking testing of the predicted inhibitors gave a high level of correlation between the ML prediction score and binding free energy.Conclusions:Currently known AR inhibitors are not used yet for patients for several reasons.We think that new predicted AR inhibitors have the potential to possess more favorable characteristics to be successfully implemented after clinical testing.Exploring new inhibitors can improve patient well-being and lower surgical complications all while decreasing long-term medical expenses.