Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Hepatic drug transporters and nuclear receptors:Regulation by therapeutic agents

The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.

Bridging larger gaps in peripheral nerves using neural prosthetics and physical therapeutic agents

Peripheral nerve injuries are relatively common and can be caused by a variety of traumatic events such as motor vehicle accidents.They can lead to long-term disability,pain,and financial burden,and contribute to poor quality of life.In this review,we systematically analyze the contemporary literature on peripheral nerve gap management using nerve prostheses in conjunction with physical therapeutic agents.The use of nerve prostheses to assist nerve regeneration across large gaps(> 30 mm) has revolutionized neural surgery.The materials used for nerve prostheses have been greatly refined,making them suitable for repairing large nerve gaps.However,research on peripheral nerve gap management using nerve prostheses reports inconsistent functional outcomes,especially when prostheses are integrated with physical therapeutic agents,and thus warrants careful investigation.This review explores the effectiveness of nerve prostheses for bridging large nerve gaps and then addresses their use in combination with physical therapeutic agents.

Novel therapeutic agents in the treatment of metastatic colorectal cancer

Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers(mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well.

Current and Future Therapeutic Agents in the Man-agement of Heart Failure

Congestive heart failure is a disease in which initially compensatory changes in cardiac , vascular, and renal functions become detrimental over time. The changes are mediated by a large number of neurohormones and cytokines. Counter-regulatory hormones also play a role, but are generally insufficient to offset the adverse effects of the neurohormones or progression of the disease. Symptoms of heart failure occurs in the 'presence of systolic dysfunction, usually documented by a decrease in ejection fraction, or can present with impaired diastolic function occasionally labeled as heart failure with preserved systolic function of the left ventricle. Heart failure and its treatment represent a medical problem of significant importance because of the high mortality associated with it despite the current therapy , which has substantial evidence of reduction in mortality and morbidity. Prevention or slowing of the progressive deterioration in function of the heart and other organs involved through utilizing new agents that affect more or different neurohormonal pathways may be beneficial and forms the focus of heart failure research and drug development. However , the multiplicity of hormonal effects mandate the use of complex therapy in the management of congestive heart failure(CHF). The new agents in addition to the conventional therapy used in the management of heart failure are; Human B-type nalriuretic peptide (in the treatment of decompensated CHF) , endothelin receptor antagonists, calcium sensitizers, neutral endopeptidase (NEP) and vasopeptidase inhibitors, vasopressin antagonists and cytokine inhibitors.

Galectin-3 prospects as a therapeutic agent for multiple sclerosis

Galectin-3 (Gal-3) in oligodendrocyte (OLG) differentiation: OLGs are the cells in charge of myelination in the central nervous system (CNS), allowing rapid conduction of the neural action potential and giving trophic support to axons. OLGs undergo a series of changes throughout their life cycle: first, upon neural stem cell comm让ment to the OLG lineage, cells referred to as OLG precursor cells (OPC) present a bipolar morphology, have proliferative and migratory capacity and express molecular markers like platelet-derived growth factor receptor alpha and neural/glial antigen 2.

A review of therapeutic agents for breast cancer with potentially radiosensitizing properties

Breast cancer is the most frequently diagnosed malignant tumor in women worldwide and the leading cause of cancer death.Radiotherapy for breast cancer is readily accepted and widely used in clinical practice.Potential limitations with radiotherapy include treatment resistance,side effects,and complications caused by high doses of irradiation.The search has been on to locate an efficacious radiosensitizer.This review summarizes six currently approved pharmaceuticals that have also been investigated for off-label use as radiosensitizers in breast cancer.

Activated aggregation-induced emission therapeutics agents for triggering regulated cell death

The induction of regulated cell death(RCD)through photo/ultrasound sensiti-zation therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors.Aggregation-induced emission(AIE)therapeutic agents generate reactive oxygen species through photo/ultrasound activation,which can synergize with RCD inducers or directly induce RCD,ultimately resulting in the death of tumor cells.The presented comprehensive review delves into recent advancements in AIE therapeutic agents designed to trigger RCD or synergize with RCD inducers,encompassing apoptosis,necroptosis,pyroptosis,immunogenic cell death,autophagy,ferroptosis,and cuproptosis.Additionally,the intricate regula-tory mechanisms through which activatory-AIE therapeutics influence distinct RCD pathways are examined.A forward-looking perspective on future developments and pertinent challenges within this exciting realm is presented,anticipating the con-tinued evolution of activatable AIE therapeutics as a transformative approach to enhance tumor therapy.

Molecular targeting agents associated with transarterial chemoembolization or radiofrequency ablation in hepatocarcinoma treatment

Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the world.According to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablation(RFA),while patients with intermediate stage HCC are usually treated by transarterial chemoembolization(TACE).TACE and RFA induce a transient devascularisation effect followed by strong neoangiogenic stimulus.In fact,after these procedures,it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A,which might contribute to accelerated progression in patients with incomplete response.Several studies have demonstrated that MAP-kinase and AKT pathways,in addition to neo-angiogenesis,have an important role in the development of HCC.In advanced HCC,anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical benefit.Actually,a number of clinical studies are ongoing testing these agents in combination with TACE or RFA.In this paper,we have reviewed the most recent preclinical and clinical results of such trials.

Evolving spectrum of diabetic wound: Mechanistic insights and therapeutic targets

Diabetes mellitus is a chronic metabolic disorder resulting in an increased blood glucose level and prolonged hyperglycemia,causes long term health consequences.Chronic wound is frequently occurring in diabetes patients due to compromised wound healing capability.Management of wounds in diabetic patients remains a clinical challenge despite many advancements in the field of science and technology.Increasing evidence indicates that alteration of the biochemical milieu resulting from alteration in inflammatory cytokines and matrix metalloproteinase,decrease in fibroblast and keratinocyte functioning,neuropathy,altered leukocyte functioning,infection,etc.,plays a significant role in impaired wound healing in diabetic people.Apart from the current pharmacotherapy,different other approaches like the use of conventional drugs,antidiabetic medication,antibiotics,debridement,offloading,platelet-rich plasma,growth factor,oxygen therapy,negative pressure wound therapy,low-level laser,extracorporeal shock wave bioengineered substitute can be considered in the management of diabetic wounds.Drugs/therapeutic strategy that induce angiogenesis and collagen synthesis,inhibition of MMPs,reduction of oxidative stress,controlling hyperglycemia,increase growth factors,regulate inflammatory cytokines,cause NO induction,induce fibroblast and keratinocyte proliferation,control microbial infections are considered important in controlling diabetic wound.Further,medicinal plants and/or phytoconstituents also offer a viable alternative in the treatment of diabetic wound.The focus of the present review is to highlight the molecular and cellular mechanisms,and discuss the drug targets and treatment strategies involved in the diabetic wound.

Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats

AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging(DW-MRI).METHODS:Thirty-seven rats with implanted liver tumors were randomized into the following three groups:(1)ZD6126,a kind of VDA;(2)ZDTHA,ZD6126 in combination with an antiangiogenic,thalidomide;and(3)control.Morphological DW-MRI were performed and quantified before,4 h and 2 d after treatment.The apparent diffusion coefficient(ADC)values were calculated separately for low b values(ADC low),high b values(ADC high)and all b values(ADC all).The tissue perfusion contribution,ADC perf,was calculated as ADC low-ADC high.Imaging findings were finally verified by histopathology.RESULTS:The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis.In addition to delaying tumor growth,ZDTHA caused tumor necrosis in an additive manner,which was verified by HE staining.Although both ADC high and ADC all in the ZD6126and ZDTHA groups were significantly higher compared to those in the control group on day 2,the entire tumor ADC high of ZDTHA was even higher than that of ZD6126,but the significant difference was not observed for ADCall between ZDTHA and ZD6126.This indicated that the perfusion insensitive ADC high values calculated from high b value images performed significantly better than ADC all for the monitoring of tumor necrosis on day 2.The perfusion sensitive ADC perf derived from ADC low by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126,compared to the ADC low at 4 h.The ADC perf could provide valuable perfusion information from DW-MRI data.CONCLUSION:The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126and thalidomide for solid tumors.

Stimuli-responsive nanocarriers for therapeutic applications in cancer

Cancer has become a very serious challenge with aging of the human population.Advances in nanotechnology have provided new perspectives in the treatment of cancer.Through the combination of nanotechnology and therapeutics,nanomedicine has been successfully used to treat cancer in recent years.In terms of nanomedicine,nanocarriers play a key role in delivering therapeutic agents,reducing severe side effects,simplifying the administration scheme,and improving therapeutic efficacies.Modulations of the structure and function of nanocarriers for improved therapeutic efficacy in cancer have attracted increasing attention in recent years.Stimuli-responsive nanocarriers penetrate deeply into tissues and respond to external or internal stimuli by releasing the therapeutic agent for cancer therapy.Notably,stimuli-responsive nanocarriers reduce the severe side effects of therapeutic agents,when compared with systemic chemotherapy,and achieve controlled drug release at tumor sites.Therefore,the development of stimuli-responsive nanocarriers plays a crucial role in drug delivery for cancer therapy.This article focuses on the development of nanomaterials with stimuli-responsive properties for use as nanocarriers,in the last few decades.These nanocarriers are more effective at delivering the therapeutic agent under the control of external or internal stimuli.Furthermore,nanocarriers with theranostic features have been designed and fabricated to confirm their great potential in achieving effective treatment of cancer,which will provide us with better choices for cancer therapy.

Glycoconjugation: An approach to cancer therapeutics

Cancer constitutes the second leading cause of death globally and is considered to have been responsible for an estimated 9.6 million fatalities in 2018.Although treatments against gastrointestinal tumors have recently advanced,those interventions can only be applied to a minority of patients at the time of diagnosis.Therefore,new therapeutic options are necessary for advanced stages of the disease.Glycosylation of antitumor agents,has been found to improve pharmacokinetic parameters,reduce side effects,and expand drug half-life in comparison with the parent compounds.In addition,glycosylation of therapeutic agents has been proven to be an effective strategy for their targeting tumor tissue,thereby reducing the doses of the glycodrugs administered to patients.This review focusses on the effect of the targeting properties of glycosylated antitumor agents on gastrointestinal tumors.

Schiff Bases as Important Class of Pharmacological Agents

Therapeutics are compounds,which do not always exhibit healing powers.They sometimes prevent or control roles.Many compounds,well known or less are treated as the therapeutic agents.Among them,there is a specific group of molecules named commonly as Schiff bases,chemically imines.Schiff bases are aldehyde-or ketone-like compounds in which the carbonyl group is replaced by an imine-HN=СН-or azomethine-NHN=СН-group,they are an important class of compounds for new drug development.Schiff base modifications so far proved to be very effective with increased efficacy and reduced toxicity.Therefore,many researchers have synthesized these compounds as target structures and evaluated their biological activity.The aim of this work was to present some interesting and promising examples of Schiff bases which exhibit biological activity.

Formation of a potential tumor therapeutic pharmaceutical ^(186)Re-bleomycin

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耐碳青霉烯类肺炎克雷伯菌感染的治疗研究

目的探讨耐碳青霉烯类肺炎克雷伯菌的抗感染治疗方案。方法回顾本院2020年2月-2021年6月住院患者检出CRKP的病例,应用SPSS软件比较CRKP患者治疗前后体温和感染标志物变化,结合病情,对治疗方案及疗效进行分析评价。结果研究纳入59名CRKP感染患者,药敏试验敏感率较高的药物有头孢他啶/阿维巴坦、替加环素、复方磺胺甲噁唑及多粘菌素。主要治疗方案为替加环素为基础的联合治疗,治疗有效率为72.88%。治疗前后患者体温、白细胞、中性粒细胞百分比和超敏C反应蛋白均较前明显下降,差异有统计学意义(P<0.05)。治疗过程中无明显不良反应发生。结论本院患者多使用替加环素联合方案治疗,疗效尚可。

超声造影预测局部晚期宫颈癌同步放化疗早期疗效的临床价值

目的 探讨超声造影(CEUS)预测局部晚期宫颈癌(LACC)患者同步放化疗(CCRT)早期疗效的临床价值。方法 选取临沂市肿瘤医院收治的LACC患者65例,于治疗前1周内及体外放疗结束后分别进行CEUS检查,通过定量分析时间-强度曲线(TIC)获得达峰时间(TP)、梯度(Grad)、曲线下面积(Area)及峰值强度(PI);测量治疗前后瘤体最大径,计算肿瘤消退率。体外放疗结束后根据治疗效果分为敏感组53例和不敏感组12例,比较两组上述参数的差异。采用Spearman相关分析法分析CEUS参数与肿瘤消退率的相关性;二元Logistic回归分析筛选预测LACC患者CCRT早期疗效的影响因素;绘制受试者工作特征(ROC)曲线分析其预测效能。结果 65例LACC患者治疗前和体外放疗结束后瘤体最大径分别为(60.7±14.6)mm、(31.2±16.9)mm,肿瘤消退率为(49.2±23.2)%。敏感组治疗前Grad、PI均低于不敏感组,差异均有统计学意义(均P<0.05);敏感组体外放疗结束后Grad、Area及PI均低于不敏感组,TP高于不敏感组,差异均有统计学意义(均P<0.001)。敏感组体外放疗结束后Grad、Area及PI均较治疗前降低,TP较治疗前升高,差异均有统计学意义(均P<0.05)。相关性分析显示,治疗前Grad、PI与肿瘤消退率均呈负相关(r=-0.602、-0.499,均P<0.05);体外放疗结束后Grad、PI与肿瘤消退率均呈负相关(r=-0.859、-0.913,均P<0.05)。二元Logistic回归分析显示,治疗前Grad、PI均为预测LACC患者CCRT早期疗效的独立影响因素(均P<0.05)。ROC曲线分析显示,治疗前Grad、PI预测LACC患者CCRT早期疗效的曲线下面积分别为0.802、0.894。结论 CEUS在预测LACC患者CCRT早期疗效中有一定的临床价值。

PAN-TB治疗策略的实施对结核病防控的意义及挑战

全球耐药结核病的防控仍面临巨大挑战,PAN-TB方案是适用于所有结核病的一线方案,即确诊活动性结核病后即启动该方案,而不需要获得患者的耐药情况。推行PAN-TB方案的目的是旨在尽快启动有效治疗,降低传播,并可以大幅度减轻结核病规划管理的复杂性。它不仅是临床治疗方法,更是公共卫生手段。本文就PAN-TB策略的定义、方案的要求、全球的研究进展,以及对于结核病防控的意义和目前面临的挑战进行阐述,以期为中国结核病的防控提供新的思路。

HP阳性慢性浅表性胃炎患者采用益生菌联合铋剂四联治疗价值探讨

目的探究幽门螺旋杆菌阳性慢性浅表性胃炎患者应用益生菌联合铋剂四联治疗的效果。方法将福建省福清市医院自2021年2月至2023年10月收治的120例HP阳性慢性浅表性胃炎患者纳入研究。采用完全随机分组法均分为试验组及对照组,每组均为60例。对照组采用铋剂四联治疗,试验组加用益生菌治疗。比较两组的治疗效果、HP转阴率、临床症状改善情况、胃肠功能水平、炎性因子水平及安全性。结果试验组治疗效果高于对照组(P<0.05);试验组HP转阴率高于对照组(P<0.05);试验组临床症状改善情况中腹胀、恶心呕吐、反酸嗳气及上腹痛症状消失时间均少于对照组(P<0.05);试验组胃肠功能中PGⅠ、PGⅡ水平均低于对照组(P<0.05);试验组胃肠功能中GAS水平高于对照组(P<0.05);试验组不良反应率低于对照组(P<0.05)。结论对比单独应用铋剂四联治疗,益生菌联合治疗能够提高HP阳性慢性浅表性胃炎患者的疗效,改善临床症状及胃肠功能,降低炎性因子水平,且不良反应较少,安全性较好。