MicroRNAs: a novel promising therapeutic target for cerebral ischemia/reperfusion injury?

To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the micro RNA（mi RNA） expression profile in rat cortex after focal cerebral ischemia/reperfusion injury using mi RNA microarrays and bioinformatic tools to systematically analyze Gene Ontology（GO） function classifications, as well as the signaling pathways of genes targeted by these differentially expressed mi RNAs. Our results show significantly changed mi RNA expression profiles in the reperfusion period after focal cerebral ischemia, with a total of 15 mi RNAs up-regulated and 44 mi RNAs down-regulated. Target genes of these differentially expressed mi RNAs were mainly involved in metabolic and cellular processes, which were identified as hub nodes of a mi RNA-GO-network. The most correlated pathways included D-glutamine and D-glutamate metabolism, the renin-angiotensin system, peroxisomes, the PPAR signaling pathway, SNARE interactions in vesicular transport, and the calcium signaling pathway. Our study suggests that mi RNAs play an important role in the pathological process of cerebral ischemia/reperfusion injury. Understanding mi RNA expression and function may shed light on the molecular mechanism of cerebral ischemia/reperfusion injury.

Design,delivery and efficacy testing of therapeutic nucleic acids used to inhibit hepatitis C virus gene expression in vitro and in vivo

Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated effectively.Toimprove this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental treatment.Antisense oligodeoxynucleotides(ODN) are

Therapeutic and Medicinal Uses of <i>Aloe vera</i>: A Review

The plant Aloe vera is used in Ayurvedic, Homoeopathic and Allopathic streams of medicine, and not only tribal community but also most of the people for food and medicine. The plant leaves contains numerous vitamins, minerals, enzymes, amino acids, natural sugars and other bioactive compounds with emollient, purgative, anti-microbial, anti inflammatory, antioxidant, aphrodisiac, anti-helmenthic, antifungal, antiseptic and cosmetic values for health care. This plant has potential to cure sunburns, burns and minor cuts, and even skin cancer. The external use in cosmetic primarily acts as skin healer and prevents injury of epithelial tissues, cures acne and gives a youthful glow to skin, also acts as extremely powerful laxative.

Mesenteric ischemia:Pathogenesis and challengingdiagnostic and therapeutic modalities

Mesenteric ischemia(MI) is an uncommon medical condition with high mortality rates. ΜΙ includes inadequate blood supply, inflammatory injury and eventually necrosis of the bowel wall. The disease can be divided into acute and chronic MI(CMI), with the first being subdivided into four categories. Therefore, acute MI(AMI) can occur as a result of arterial embolism, arterial thrombosis, mesenteric venous thrombosis and nonocclusive causes. Bowel damage is in proportion to the mesenteric blood flow decrease and may vary from minimum lesions, due to reversible ischemia, to transmural injury, with subsequent necrosis and perforation. CMI is associated to diffuse atherosclerotic disease in more than 95% of cases, with all major mesenteric arteries presenting stenosis or occlusion. Because of a lack of specific signs or due to its sometime quiet presentation, this condition is frequently diagnosed only at an advanced stage. Computed tomography(CT) imaging and CT angiography contribute to differential diagnosis and management of AMI. Angiography is also the criterion standard for CMI, with mesenteric duplex ultrasonography and magnetic resonance angiography also being of great importance. Therapeutic approach of MI includes both medical and surgical treatment. Surgical procedures include restoration of the blood flow with arteriotomy, endarterectomy or anterograde bypass, while resection of necrotic bowel is always implemented. The aim of this review was to evaluate the results of surgical treatment for MI and to present the recent literature in order to provide an update on the current concepts of surgical management of the disease. Mesh words selected include MI, diagnostic approach and therapeutic management.

Argon: a novel therapeutic option to treat neuronal ischemia and reperfusion injuries?

Neuronal injury and neuroprotection：Ischemia and reperfusion injuries in neuronal cells such as acute ischemic stroke-represent the third leading cause of death in the world.Current therapeutic concepts mainly aim to re-establish cerebral blood flow within a time window of less than 3 hours with the goal of limiting secondary brain injury.

Continuous Wear of Hydrogel Contact Lenses for Therapeutic Use

Purpose: To investigate the efficacy and complications of continuous wear of etafilcon A for therapeutic use. Materials and Methods: The subjects were 228 eyes of 219 outpatients prescribed contact lens (CL) for one week of continuous therapeutic wear during 10 years. The reason for prescription of CLs, the primary disease, the duration of CL wear and the complications were assessed retrospectively. Results: The predominant reason for prescription of CLs was relief of pain or a foreign-body sensation (62.3%) and protection of the corneal epithelium (20.6%). The primary disease was post-penetrating keratoplasty (36.8%), followed by corneal epithelial erosion (14.5%), post-lamellar keratoplasty (14.0%) and bullous keratopathy (12.2%). The average duration of wearing single lens was 6.5 ± 3.2 days. The average duration of wearing CLs in total was 9.2 ± 10.7 months. The most frequent problem associated with continuous wear of CLs was their dropping out of CLs (12.3%). The complications associated with CLs included conjunctivitis with papillary hyperplasia, corneal erosion and superficial punctate keratitis, but corneal ulcer and corneal infiltrates were not found. Conclusion: Serious complications were not shown changing the lenses every week to keep to the prescribed time limit for continuous therapeutic wear, even if corneal epithelial barrier function is impaired.

Neuroprotective mechanisms and translational potential of therapeutic hypothermia in the treatment of ischemic stroke

Stroke is a leading cause of disability and death,yet effective treatments for acute stroke has been very limited.Thus far,tissue plasminogen activator has been the only FDA-approved drug for thrombolytic treatment of ischemic stroke patients,yet its application is only applicable to less than 4–5% of stroke patients due to the narrow therapeutic window（〈 4.5 hours after the onset of stroke） and the high risk of hemorrhagic transformation.Emerging evidence from basic and clinical studies has shown that therapeutic hypothermia,also known as targeted temperature management,can be a promising therapy for patients with different types of stroke.Moreover,the success in animal models using pharmacologically induced hypothermia（PIH） has gained increasing momentum for clinical translation of hypothermic therapy.This review provides an updated overview of the mechanisms and protective effects of therapeutic hypothermia,as well as the recent development and findings behind PIH treatment.It is expected that a safe and effective hypothermic therapy has a high translational potential for clinical treatment of patients with stroke and other CNS injuries.

Comparison of long-lasting therapeutic effects between succimer and penicillamine on hepatolenticular degeneration

AIM To compare the long term effect of succimer (Suc) with that of penicillamine (Pen) in treating hepatolenticular degeneration (HLD). METHODS One hundred and twenty patients with HLD were divided into 2 groups. Group A ( n =60) received Suc 750mg , po. bid. Group B ( n =60) received Pen 250mg , po. qid. The period of maintenance treatment varied from 6 months to 3 years, averaging 1 5 years. Symptoms and therapeutic effects were evaluated by modified Goldstein scale. RESULTS The total effectiveness of group A in two different periods of treatment were 80% and 85% respectively, higher than those of group B (58% and 59% respectively) ( P <0 05). Suc also had obvious curative effects for the patients who failed in the use of Pen. There were fewer side effect in group A than in group B ( P <0 05). Suc and Pen could increase urinary copper excretion effectively and continually. CONCLUSION Suc is more effective and safer than Pen. Clinically, it can replace Pen as first choice drug for long term maintenance therapy of HLD.

Functional dyspepsia of ulcer-dysmotility type:clinical incidence and therapeutic strategy

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Therapeutic role of template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract

Lymphadenectomy for urothelial carcinoma of the upper urinary tract has attracted the attention of physicians. The mapping study of lymphatic spread has shown that a relatively wide area should comprise the regional nodes for tumors of the right renal pelvis or the right upper two-thirds of the ureter. A prospective study showed that an anatomical templatebased lymphadenectomy significantly improved patient survival in tumors of the renal pelvis. This benefit was more evident for patients with p T2 stage tumors or higher. The risk of regional node recurrence is significant reduced by template-based lymphadenectomy,which is likely to be associated with improved patient survival. The removal of lymph node micrometastases is assumed to be the reason for therapeutic benefit following lymphadenectomy. The number of resected lymph nodes can be used to assess the quality of lymphadenectomy,but not to determine the extent of lymphadenectomy. The guidelines currently recommend lymphadenectomy for patients with muscle-invasive disease,even though the current recommendation grades are still low. The present limitation of lymphadenectomy is the lack of standardization of the extent of lymphadenectomy and the randomized trials. Further studies are warranted to collect the evidence to support lymphadenectomy.

Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?

Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and cognition.Clinical guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic encephalopathy.The clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong evidence.There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy.Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia.In this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.

Optimal therapeutic dose and time window of picroside II in cerebral ischemic injury

A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside Ⅱ inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows： （1） 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; （2） 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; （3） 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and （4） 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit.

To Optimize the Therapeutic Dose and Time Window of Picroside II in Cerebral Ischemic Injury in Rats by Orthogonal Test

The paper aims to optimize the therapeutic dose and time window of picroside II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitonenally at different ischemic time with different dose. The concentrations of neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic protein (MBP) in serum were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The results indicated that best therapeutic time window and dose of picroside II in cerebral ischemic injury were ischemia 1.5 h with 20 mg/kg body weight according to the concentrations of NSE, S100B and MBP in serum. It is concluded that according to the principle of lowest therapeutic dose with longest time window, the optimized therapeutic dose and time window are injecting picroside II intraperitonenally with 20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats.

The anti-inflammatory effect of picroside II and the optimizing of therapeutic dose and time window in cerebral ischemic injury in rats

The aim is to optimize the anti-inflammatory effect and the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods in 30 Wistar rats. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different dose. The concentrations of aquaporins 4 (AQP4), matrix metalloproteinases9 (MMP9) and cyclooxygenase 2 (COX2) in serum and brain tissue were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The best therapeutic time window and dose of picroside II in cerebral ischemic injury were 1) ischemia 2.0 h with 20 mg/kg and 1.5 h with 20 mg/kg body weight according to the concentration of AQP4 in serum and brain tissue;2) ischemia 1.5 h with 20 mg/kg and ischemia 2.0 h with 20 mg/kg according to the concentrations of MMP9 in serum and brain tissue;and 3) ischemia 1.5 h with 10 mg/kg and ischemia 1.5 h with 20 mg/kg according to the concentrations of COX2 in serum and brain tissue respectively. According to the principle of the lowest therapeutic dose with the longest time window, the optimized therapeutic dose and time window were injecting picroside II intraperitoneally with 10 - 20 mg/kg body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury.

A mimic of soft tissue infection: intra-arterial injection drug use producing hand swelling and digital ischemia

BACKGROUND: Inadvertent intra-arterial injection of illicit substances is a known complication of injection drug use and can lead to severe complications, including infection, ischemia and compartment syndrome. Identifying complications of intra-arterial injection can be difficult, as clinical manifestations overlap with other more common conditions such as cellulitis and soft tissue infection, and a history of injection drug use is frequently not disclosed.METHODS: A 37-year-old male patient presented with 24 hours of right hand pain, erythema and swelling. Despite classic "track marks", he denied a history of injection drug use, and vascular insults were not initially considered. After failing to respond to three days of aggressive treatment for suspected deep-space infection, an arteriogram demonstrated findings consistent with digital ischemia of embolic etiology.RESULTS: As a result of the delay in diagnosis, the lesion was not amenable to reperfusion and the patient required amputation of the distal digit.CONCLUSION: Practitioners should be alert to the possibility of intra-arterial injection and resulting complications when evaluating unusual extremity infections or unexplained ischemic symptoms, even in the absence of a definite history of injection drug use.

Therapeutics administered during ex vivo liver machine perfusion:An overview

Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI),as these"marginal"organs are particularly vulnerable to IRI during the process of procurement,preservation,surgery,and post-transplantation.In this review,we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process.These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway,utilizing defatting cocktails,and administering classes of agents such as vasodilators,anti-inflammatory drugs,human liver stem cell-derived extracellular vesicles,and δ-opioid agonists in order to reduce the damage of IRI.Ex vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ,effectively deliver substrates and oxygen required for cellular metabolism,therapeutically administer pharmacological or cytoprotective agents,and continuously monitor organ viability during perfusion.The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies.While novel therapeutic approaches to combat IRI are being developed through basic science research,their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.

The Neuroprotective Effect of Picroside II and Its Best Therapeutic Dose and Time Window in Cerebral Ischemic Injury in Rats

Objective: To study the neuroprotective effect of picrosede II and explore the best therapeutic dose and time window according to orthogonal design in cerebral ischemic injury in rats. Methods: The forebrain ischemia rat models were established by bilateral common carotid artery occlusion (BCCAO) method. The successful models were randomly grouped according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different doses. The contents of neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic protein (MBP) in serum and brain tissue were determined by enzyme linked immunosorbent assay (ELISA) to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. Results: The best therapeutic time window and dose of picroside II in cerebral ischemic injury may be 1) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg body weight according to the content of NSE in serum and brain tissue respectively, 2) ischemia 1.5 h with 20 mg/kg according to the content of S100B in both serum and brain tissue, and 3) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg according to the content of MBP in serum and brain tissue respectively. Conclusion: Based on the principle of the minimization of therapeutic drug dose and maximization of therapeutic time window, the optimal composition of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury should be achieved by injecting picroside II intraperitoneally with 10-20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats.

Blastocystis hominis as a cause of chronic diarrhea in low-resource settings:A systematic review

BACKGROUND Blastocystis hominis(B.hominis),an anaerobic unicellular protist parasite,is known for its diverse clinical manifestations upon infecting the human gastrointestinal tract.Although globally distributed,it is particularly prevalent in developing nations.Examining the symptoms and treatment outcomes of B.hominis infection in low-resource settings holds immense significance,providing healthcare practi-tioners with valuable insights to enhance patient care.AIM To synthesize existing evidence on the symptomatology and treatment outcomes of B.hominis infection in low-resource settings.METHODS Following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines,a systematic review was conducted.The search spanned electronic databases including PubMed,Scopus,and Google Scholar.After a comprehensive screening process,a thorough examination of the papers,adhering to inclusion and exclusion criteria,and data extraction from eligible studies was conducted.The findings underwent summarization through simple descriptive analysis.RESULTS The search yielded 1200 papers,with 17 meeting inclusion criteria.Chronic diarrhea due to B.hominis infection was reported in only two studies,while abdominal pain,diarrhea,flatulence,constipation,and nausea/vomiting emerged as the most commonly documented symptoms.Recovery rates after one week of treatment ranged from 71.8%to 100%,and after two weeks,from 60%to 100%.CONCLUSION In low-resource settings,chronic diarrhea resulting from B.hominis infection is infrequent.Common symptoms include abdominal pain,diarrhea,flatulence,constipation,and nausea/vomiting.Post-treatment,clinical outcomes are notably favorable,supporting the recommendation for treatment.Metronidazole is advocated as the first-line agent,with consideration for switching to a second-line option in cases of treatment failure or poor response.

Clinacanthus nutans:a review of the medicinal uses,pharmacology and phytochemistry

Clinacanthus nutans Lindau is known as snake grass belonging to the Acanlhaceae family.This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes,insects and snake bites,lesions caused by herpes simplex virus,diabetes,and gout in Malaysia.Indonesia.Thailand and China.Phylochemieal investigations documented the varied contents of bioaclive compounds from litis plant namely flavonoids,glycosides,glycoglyeerolipids.cerebrosides and monoacylmonogalatosylglycerol.The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory,antiviral,antioxidant,and anti-diabetic activities.The lindings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions.However,further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability tor future drugs.This review summarizes the medicinal uses,phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work.

Protective mechanisms of picroside Ⅱ on aquaporin-4 expression in a rat model of cerebral ischemia/reperfusion injury

BACKGROUND： Aquaporin-4 （AQP-4） over-expression following cerebral ischemia results in cerebral edema. Picroside Ⅱ has been shown to exhibit a neuroprotective effect on neuronal apoptosis. However, few reports have addressed the neuroprotective mechanisms and therapeutic times following cerebral ischemic reperfusion injury. OBJECTIVE： To explore the neuroprotective effects and ideal treatment window for picroside Ⅱ treatment of middle cerebral artery occlusion and reperfusion injury in rats. DESIGN, TIME AND SETTING; A randomized, controlled, animal experiment was performed at Institute of Cerebrovascular Diseases, Qingdao University Medical College from September 2008 to May 2009. MATERIALS： Picroside II was purchased from Tianjin Kuiqing Medical Technology, China. METHODS： A total of 165 adult, healthy, male, Wistar rats were randomly assigned to sham-surgery （n = 15）, model （n = 75）, and treatment groups （n = 75）. Rats in the model and treatment groups underwent middle cerebral artery occlusion and reperfusion through the use of an intraluminal monofilament suture on the left external-internal carotid artery, The treatment group was injected with 1.0% picroside Ⅱ （10 mg/kg） into the tail vein, and the model and sham-surgery groups were injected with 0.1 mol/L phosphate buffered saline （250 μL）. MAIN OUTCOME MEASURES： Neurological functional scores were evaluated using the Longa＇s method; cerebral infarction volume was detected through the use of tetrazolium chlodde staining; cellular apoptosis was determined through the use of the in situ end-labeling method; aquaporin-4 expression was measured using fluorescence labeling analysis and reverse transcription polymerase chain reaction technique. RESULTS： At 0.5 hour following cerebral ischemic injury, neurological functional scores were low, and a small infarction focus was detected in the ischemic cortex of the model group. Along with prolonged ischemia and an increased number of apoptosis-positive cells, AQP-4 mRNA and protein expression was increased. At 1-2 hours after ischemia, neurological scores and infarction sizes were significantly increased in the model group. Apoptotic-positive cells were widespread in the ipsilateral cortex and stdatum. In addition, AQP-4 mRNA and protein expression levels were increased. Picroside II treatment significantly decreased neurological scores and infarction volume, and reduced AQP-4 mRNA and protein expression levels compared with the model group （P 〈 0.05 or P 〈 0.01）. At 1 hour after ischemia, the therapeutic effect of picroside Ⅱ was notable （P 〈 0.01）. CONCLUSION： Picroside Ⅱ played a protective role in cerebral ischemic reperfusion injury by inhibiting apoptosis and regulating AQP-4 expression. The best therapeutic time window was 1 hour after cerebral ischemic reperfusion.