Application of Enzyme Inhibition Therapy in the Management/Treatment of Neurological Conditions, Diseases, and Disorders

Enzyme inhibition therapy uses specific molecules to inhibit enzyme activity, targeting disease-related enzymes in medical treatments like cancer treatment and infectious disease management. Different types of inhibitors, competitive and non-competitive, bind to different sites and alter enzyme function. The success of this therapy depends on the inhibitor’s specificity and delivery to the target site. Further research could lead to more effective treatments. Nowadays, the majority of medications are enzyme inhibitors and are in the clinical or pre-clinical stages of drug development. Enzyme inhibitors are often prescribed medications for a variety of illnesses, including neurological problems. There is only symptomatic therapy available for many neurological conditions, particularly neuro-degenerative disorders, as opposed to therapy based on knowledge of the underlying mechanisms of these diseases. Enzyme inhibitors are useful as they block the function of certain enzymes whose aberrant activity could be contributing to the illness. They also alleviate the symptoms and stop the disease’s progression. This review discusses the mechanism of action of several enzyme inhibitors that have been prescribed as medications for neurological illnesses as well as some that are still in research stages.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Effects of Different Fertilization Treatments on Soil Microbial Biomass,Soil Enzyme Activities and Related Nutrients in Continuous-cropping Sugarcane Field

[Objective] This study was conducted to expound the fertility improvement effect in continuous-cropping sugarcane field and provide reference for establishment of rational sugarcane fertilization system and improvement of soil quality in continuous-cropping sugarcane field. [Method] The soil in the experimental region is latosolic red soil which was planted with sugarcane for 11 years continuously, and 8 treatments including sole application of chemical fertilizers, sole application of organ- ic fertilizer, and combined application of organic fertilizer and chemical fertilizers were designed according to different fertilization measures. The effects of different fertilization treatments on soil microbial biomass, soil enzyme activities and related fertility factors were determined. [Result} Different fertilization treatments all showed soil microbial biomass N, C and P and activities of soil acid phosphatase, catalase, sucrase and urease higher than the CK. Soil microbial biomass N increased by 5.56%-67.13%, soil microbial biomass C increased by 4.01%-20.40%, and soil mi- crobial biomass P increased by 6.39%-67.02%. The activity of acid phosphatase was improved by 12.96%-35.19%, the activity of catalase was improved by 18.24% -78.93%, the activity of sucrase was improved by 3.00%-42.00%, and the activity of urease was improved by 1.21%-23.43%. However, the soil nutrients of different fertilization treatments increased non-significantly （P〉0.05）. Soil microbial biomass N, C and P and activities of acid phosphatase, catalase and urease were in significant （P〈0.05） or very significant correlation （P〈0.01） with contents of soil rapidly available P, rapidly available K and total N. [Conclusion] The evaluation of improvement of soil fertility in continuous-cropping sugarcane field using soil microbial biomass and enzyme activities as indexes is more comprehensive and sensitive.

Reduction in Activity/Gene Expression of Anthocyanin Degradation Enzymes in Lychee Pericarp is Responsible for the Color Protection of the Fruit by Heat and Acid Treatment

Heat and acid treatments were reported to be a promising substitute for SO2 fumigation in color protection of postharvest lychee （Litchi chinensis） fruits, but the mechanism was not clear. In the present study, hot water （70℃） dipping followed by immersion in 2% HC1 （heat-acid） substantially protected the red color of the fruit during storage at 25℃ and inhibited anthocyanin degradation while hot water dipping alone （heat） led to rapidly browning and about 90% loss in anthocyanin content. The pH values in the pericarp of the heat-acid treated fruit dropped to 3.2, while the values maintained around 5.0 in the heat-treated and control fruit. No significantly different pH values were detected among the arils of heat-acid, heat treated and control fruit. Heat-acid treatment dramatically reduced the activities of anthocyanin degradation enzyme （ADE）, peroxidase （POD） and polyphenol oxidase in the pericarp. A marked reduction in LcPOD gene expression was also detected in heat-acid treated fruit, in contrast, induction was found in heat treated fruit. The pericarp of heat-acid treated fruit exhibited significantly lower respiration rate but faster water loss than that of the untreated or heat treated fruit. Taken together, heat treatment triggered quick browning and anthocyanin loss in lychee fruit, while heat-acid treatment protected the fruit color by a great reduction in the activities/gene expression of anthocyanin degradation enzymes and acidification of lychee pericarp.

Mechanism and Application of Enzyme Treatment on Wool

Protease treatments on wool have its inherent defect in shrink-proofing because protease will decompose wool through cell membrane complex （CMC）. In order to solve this problem, mechanism of enzyme treatments on wool was adequately analyzed and possible enzyme applications were discussed. The mechanism of enzyme treatment on wool was analyzed through weight loss, strength, scanning electron microscopy （SEM）, electrophoresis, sodium dodecyl sulfate polyacrylamide gel electrophoresis （ SDS- PAGE）, and amino acids composition. Based on the results, a possible novel multifunetional enzyme treatment on wool to achieve shrink-resistance was proposed. In order to shorten enzyme treatment time, the rate of proteolysis of wool was investigated. Considering the specificity of proteases, wool composition, and structure of dyes, a better enzyme pretreatment before dyeing to get better dyeabflity and lower dyeing temperature was discussed.

Alleviation of Adverse Effects of Salt Stress in Wheat Cultivars by Foliar Treatment with Antioxidant 2—Changes in Some Biochemical Aspects, Lipid Peroxidation, Antioxidant Enzymes and Amino Acid Contents

Ascobin (compound composed of ascorbic acid and citric acid) is considered one of exogenous protectants which may alleviate the harmful effects of salinity stress. Pot experiments were performed at the screen greenhouse of National Research Centre, Cairo, Egypt to study the effect of foliar treatment of two cultivars of wheat plant with different concentrations of ascobin (0, 200, 400 and 600 mg/l) on some biochemical parameters, antioxidant enzymes, element contents and amino acid constituents of two cultivars of wheat plant grown under different salinity levels (0.0, 3000 and 6000 mg/l) in 2011/2012 and 2012/2013. Salinity with different concentrations levels increased phenolic compounds contents of the two wheat cultivars. The activities of antioxidant enzymes (SOD, CAT, POD, PPO, AXP and GR) dramatically increased due to salinity stress. Amino acid content was increased in cultivar Sids 1, while the content was decreased in cultivar Giza 168 in all salinity treatments. Increments in the above mentioned parameters compared to the untreated plants at normal and stressed conditions. The magnitude of increments was much more pronounced in response to 600 mg/l of ascobin. It could be concluded that, foliar treatment of wheat cultivars with ascobin could partially alleviate the harmful effect of salinity especially at the lower levels of salinity of the two cultivars of wheat at most of the studied parameters.

Effect of jasmonate treatments on leaves of Rosa rugosa‘Plena’and detoxification enzymes and feeding of adult Monolepta hieroglyphica

To study the effect of jasmonates(JAs)on the resistance of economic forest plants to insects,R osa rugosa‘Plena'leaves were treated with 1 mmol/L jasmonic acid(JA),methyl jasmonate(MeJA)and Z-jasmone,then the content of tannin and total phenol in leaves and the feeding area of Monolepta hieroglyphica adults on leaves were measured.Changes in the activities of detoxification enzymes in adult M.hieroglyphica that had fed on leaves treated with JAs were also studied.Tannin and total phenol levels in leaves increased significantly after treatment with JAs,and tannin level was 1.36–1.55-fold higher than in the control after treatment with 1 mmol/L MeJA.The total content of phenol in leaves treated with 1.0 mmol/L Z-jasmone increased by 1.33–2.20-fold compared with those of the control.The activities of detoxification enzymes in adults were inhibited to differing degrees:activity of alkaline phosphatase(AKP)first increased,then decreased;the activities of acid phosphatase(ACP),glutathione S-transferases(GSTs)and carboxylesterase(CarE)following treatment with 1 mmol/L MeJA were significantly reduced and were 22%–31%,11%–26%,and 11%–31%lower than those of the control,respectively.Moreover,the feeding area of adult M.hieroglyphica on the leaves treated with JAs was significantly reduced(P<0.05).The feeding area of economic forest R.rugosa‘Plena'leaves treated with 1 mmol/L MeJA decreased by 17%–43%compared with that of the control.Moreover,the decrease in the adult M.hieroglyphica feeding area was highly positively correlated with the content of tannin and positively correlated with the contents of total phenol of economic forest R.rugosa‘Plena'leaves.The reduced feeding area of adult M.hieroglyphica was highly negatively correlated with the activities of AKP and ACP and negatively correlated with those of the GSTs.In conclusion,the use of 1 mmol/L MeJA can noticeably decrease the deleterious effects of adult M.hieroglyphica.

Effect of Different Treatment Rapeseeds on Activity of Cellulose Enzyme in Sheep

The purpose of the experiment is to research the effect of different rapeseed treatments feeding on activity of cellulose enzyme in sheep. Eight male adults of semi-fine wool sheep breeds with the same weight and permanent rurnen cannulas were selected according to 4×4 Latin square design to determine the effect of different rapeseed treatment groups including crushed rapeseed, whole rapeseed, extruded rapeseed （dietary lipid content of =67 g·kg^-1） and control group （dietary lipid content of =30 g·kg^-1） on activity dynamic variation of ruminal celluolytic enzyme in sheep. The results showed that ruminal fluid pH matched up to the condition of fiber degradation and growth of cellulolytic bacterium when fed four diets; but there was significant difference （P〈0.05） for the activity of microcrystalline cellulose, glucanase, salicin enzyme involved in ruminal fiber degradation after fed 2, 4, 6 h.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Enzyme measurements for risk evaluations in sewage treatment plants

Objectives: Work in sewage treatment plants may cause health problems in terms of airways symptoms, unusual tiredness, fever, and diarrhoea. The presence of such symptoms has been related to bacterial endotoxin. The project was undertaken to assess if risk evaluations could be performed by measuring the amounts of two different microbial enzymes and to evaluate their relation to endotoxin. Methods: Measurements were performed at 120 work sites in 10 different sewage treatment plants of varying age and capacity. The content of N-acetyl-hexosaminidase (NAHA), bacterial hydrolase (BH) and endotoxin was measured in sewage water and in airborne samples. Results: There was a close relationship between endotoxin and NAHA, both in the water itself and in air samples. Generally exposure levels were low but higher at work sites where the water or sludge was agitated or when repairing pumps and cleaning basins. Conclusions: Measurements of NAHA are suitable to determine risk exposures in sewage treatment plants. Such measurements are faster and cheaper than measures of endotoxin. A level of 50-70 U/m3 is suggested as a risk threshold. Further work is required to define more precise threshold limit values.

Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Chronic Alcohol Consumption Affects Serum Enzymes Levels in the HIV-Infected Patients on Stavudine (d4T)/Lamivudine (3TC)/Nevirapine (NVP) Treatment Regimen

Chronic alcohol use is a common problem globally among the HIV-infected patients on ARV treatment regimens, leading to severe liver damage and increase in serum enzymes. The study determined effect of chronic alcohol intake on serum enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)) in HIV-infected patients on d4T/3TC/NVP treatment regimen in Uganda using the WHO alcohol use disorders’ identification test (AUDIT) tool and chronic alcohol use biomarkers (ALT, AST, GGT, AST/ALT ≥ 2.0 and mean corpuscular volume (MCV)). A case control study using repeated measure design with serial measurements model was used. Alcohol use biomarkers were used to standardize the gender differences in alcohol use. A total of 41 patients (21 alcohol group and 20 control group) were followed up for 9 months with blood sampling done at 3 month intervals. The serum enzymes’ levels were determined by using the Cobas Intergra 400 Plus analyzer system. The mean GGT levels were higher in chronic alcohol use group as compared to control group in both groups. The levels were above reference ranges during 6 month and three times higher during 9-month follow-up period for both chronic alcohol use self reporting WHO AUDIT tool and biomarkers’ groups. Generally, the mean AST, ALT and AST/ALT levels were slightly higher in alcohol use group as compared to control group and were slightly higher in both groups as compared to reference ranges during the 9 month follow-up period. Chronic alcohol consumption by HIV-infected patients on d4T/3TC/NVP drug regimen increased GGT and AST/ALT serum enzyme levels and hence was used as chronic alcohol use biomarkers.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.