bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleic Acid Delivery System by the Combination of Lipid bubbles and Ultrasound
Authors: Endo-Takahashi Yoko , Maruyama Kazuo , Negishi Yoichi 
Published: August 2018

Background:
RNA interference (RNAi)-based therapy has gained attention because of its potent genesilencing
effect and high specificity. However, the efficient delivery of nucleic acids to the target site is a major
challenge to the clinical implementation. Recently, ultrasound-mediated gene delivery systems have been developed
and attracted interest due to its safety and site-specificity. By the combination with contrast agents, called
microbubbles, not only the delivery effects but also the imaging effects are significantly enhanced. We developed
lipid bubbles (LBs) entrapping an ultrasound contrast gas to enhance the efficacy of ultrasound-mediated delivery
and imaging. In this review, we summarize ultrasound-mediated nucleic acid delivery systems and discuss the
possibility of combining LBs and ultrasound for RNAi-based therapies.

Methods:
We prepared polyethylene glycol-modified liposomes and entrapped an echo-contrast gas within the
liposomes. Small interfering RNA (siRNA) were transfected into cells and muscles using LBs and ultrasound.
Moreover, we also developed nucleic acid-loaded LBs using cholesterol-conjugated siRNA or positively-charged
lipid for an efficient systemic delivery of siRNA and microRNA. The usability of LBs for RNA delivery system
was evaluated by the silencing effects of target genes and the therapeutic effects on ischemia hind limb.

Results:
A combination of LBs and therapeutic ultrasound was able to enhance the gene silencing effects by
siRNA. Nucleic acid-loaded LBs were able to efficiently deliver siRNA or microRNA by systemic administration.
A combination of LBs and diagnostic ultrasound also enhanced the imaging efficiency. Using a hindlimb
ischemia mouse model, microRNA-loaded LBs could lead to increased angiogenic factors and improved blood
flow.

Conclusion:
Ultrasound technology is widely used in clinical settings not only for diagnosis but also for therapy.
Ultrasonic devices are being actively developed. Computer-controlled ultrasound systems can provide precise
exposure to the target site. The combination of precise ultrasound exposure and LBs might be useful for target
site-specific nucleic acids delivery, and holds potential to be developed into a beneficial therapeutic and diagnostic
system for various diseases.
Nanostructured Hyaluronic Acid-based Materials for the Delivery of siRNA
Authors: Shah Keval , Chawla Sunita , Gadeval Anuradha , Reddy Goutham , Maheshwari Rahul , Kalia Kiran , Tekade Rakesh Kumar 
Published: August 2018

Background:
The search for the effective treatment strategies to combat a disease that is characterized
by abnormal cell growth and known as cancer is still required to reach its destiny. To address the problem, recently
several gene therapies based on novel RNA interference (RNAi) have been proposed such as siRNA, micro
RNA, shRNA, etc. out of which, siRNAs (silencing RNA) promises to show significant progress in pharmacotherapy,
including considerable expansion of the druggable target space and the possibility of treating cancer.

Methods:
This review aims to uncover the hyaluronic acid (HA) and HA-hybridized nanoplatforms for siRNA
delivery systems with a particular focus on the discussion of available reports while addressing the future potential
of HA-based treatment strategies.

Results:
HA modified siRNA delivery, as promised, provided better targeting potential in many types of cancers.
In addition, it was able to modify the release of siRNA as well. Toxicity of HA is well mentioned however, the
loophole is yet to be filled by exploring various remedies for overcoming toxicity.

Conclusion:
To overcome the problems associated with these emerging genetic tools, investigators have employed
glycosaminoglycan HA-based biopolymers. This biopolymer offers a variety of properties such as biodegradability,
biocompatibility, aqueous solubility, viscoelasticity, and non-immunogenicity.
Gene Silencing using siRNA for Preventing Liver Ischaemia-Reperfusion Injury
Authors: Marinho H. Susana , Marcelino Paulo , Soares Helena , Corvo Maria Luísa 
Published: August 2018

Background:
Ischaemia-reperfusion injury (IRI), a major complication occurring during organ transplantation,
involves an initial ischemia insult, due to loss of blood supply, followed by an inflammation-mediated
reperfusion injury. A variety of molecular targets and pathways involved in liver IRI have been identified. Gene
silencing through RNA interference (RNAi) by means of small interference RNA (siRNA) targeting mediators of
IRI is a promising therapeutic approach.

Objective:
This study aims at reviewing the use of siRNAs as therapeutic agents to prevent IRI during liver transplantation.

Method:
We review the crucial choice of siRNA targets and the advantages and problems of the use of siRNAs.

Results:
We propose possible targets for siRNA therapy during liver IRI. Moreover, we discuss how drug delivery
systems, namely liposomes, may improve siRNA therapy by increasing siRNA stability in vivo and avoiding
siRNA off-target effects.

Conclusion:
siRNA therapeutic potential to preclude liver IRI can be improved by a better knowledge of what
molecules to target and by using more efficient delivery strategies.
Effect of Geographical Location and Type of Extract on Total Phenol/Flavon Contents and Antioxidant Activity of Different Fruits Extracts of Withania somnifera
Authors: Adhikari Lokesh , Kotiyal Rupali , Pandey Mukesh , Bharkatiya Meenakshi , Sematy Ajay , Semalty Mona 
Published: August 2018

Background:Withania somnifera (family solanaceae) is a well-investigated medicinal plant which is also called Indian ginseng due to its wide spectrum of medicinal properties. The contents and activity of the plant may vary depending on the habitat and part of the plant and the solvent used for extraction. The present study deals with the comparative chemical analysis and in vitro antioxidant activity of methanolic fruits extracts and its subfractions (in ethyl acetate, butanol and water) of W. somnifera collected from two different geographical locations.Methods:In the present study, Withania somnifera fruits were collected from two different geographical locations (Uttarakhand and Rajasthan). The different fruit extracts were prepared and studied for total phenolic contents and total flavone contents. The in vitro antioxidant activity was assessed by DPPH free radical scavenging assay and peroxide scavenging assay.Results:Methanol extract of W. somnifera Uttarakhand and ethyl acetate subfraction of W. somnifera Rajasthan showed the highest amount of Total Phenolic Contents (TPC). In W. somnifera Uttarakhand, ethyl acetate extract showed the highest amount of Total flavonoids while in W. somnifera Rajasthan, methanol extract was found to be the richest in flavonoids. Methanolic extract of W. somnifera Uttarakhand showed the highest free radical scavenging activity while in W. somnifera Rajasthan, the highest antioxidant activity was shown by the methanolic extract followed by butanolic extract, water extract and then ethyl acetate. In the peroxide scavenging assay of antioxidant activity, water extract of W. somnifera Uttarakhand showed the highest activity, while in W. somnifera Rajasthan, ethyl acetate extract showed highest scavenging activity.Conclusion:It was concluded that the geographical location exerts a vital effect on the presence of active constituents and also on the antioxidant potential of W. somnifera.
Identification and Ranking of Clinical Compounds with Activity Against Log-phase Growing Uropathogenic Escherichia coli
Authors: Niu Hongxia , Yee Rebecca , Cui Peng , Zhang Shuo , Tian Lili , Shi Wanliang , Sullivan David , Zhu Bingdong , Zhang Wenhong , Zhang Ying 
Published: August 2018

Background:
Uropathogenic Escherichia coli (UPEC) is a major cause of Urinary
Tract Infections (UTIs). Due to increasing antibiotic-resistance among UPEC bacteria, new
treatment options for UTIs are urgently needed.

Objective:
To identify new agents targeting growing bacteria that may be used for the treatment of
antibiotic-resistant UTIs.

Methods:
We screened a clinical compound library consisting of 1,524 compounds using a high
throughput 96-well plate assay and ranked the activities of the selected agents according to their
MICs against the UPEC strain UTI89.

Results:
We identified 33 antibiotics which were active against log-phase clinical UPEC strain
UTI89. Among the selected antibiotics, there were 12 fluoroquinolone antibiotics (tosufloxacin,
levofloxacin, sparfloxacin, clinafloxacin, pazufloxacin, gatifloxacin, enrofloxacin, lomefloxacin,
norfloxacin, fleroxacin, flumequine, ciprofloxacin), 15 beta-lactam or cephalosporin antibiotics
(cefmenoxime, cefotaxime, ceftizoxime, cefotiam, cefdinir, cefoperazone, cefpiramide,
cefamandole, cefixime, ceftibuten, cefmetazole, cephalosporin C, aztreonam, piperacillintazobactam,
mezlocillin), 3 tetracycline antibiotics (meclocycline, doxycycline, tetracycline), 2
membrane-acting agents (colistin and clofoctol), and 1 protein synthesis inhibitor (amikacin).
Among them, the top 7 hits were colistin, tosufloxacin, levofloxacin, sparfloxacin, clinafloxacin,
cefmenoxime and pazufloxacin, where clinafloxacin and pazufloxacin were the newly identified
agents active against UPEC strain UTI89. We validated the key results obtained with UTI89 on
two other UTI strains CFT073 and KTE181 and found that they all had comparable MICs for
fluoroquinolones while CFT073 and KTE181 were more susceptible to cephalosporin antibiotics
and tetracycline antibiotics but were less susceptible to colistin than UTI89.

Conclusion:
Our findings provide possible effective drug candidates for the more effective
treatment of antibiotic-resistant UTIs.
The Effect of Neuropathic Pain Symptoms on Remission in Patients with Early Rheumatoid Arthritis
Authors: Salaffi Fausto , Di Carlo Marco , Carotti Marina , Sarzi-Puttini Piercarlo 
Published: August 2018

Background:The presence of neuropatic pain (NeP) is common in subjects with established Rheumatoid Arthritis (RA), and it can influence the disease remission. These aspects have not been investigated in patients with Early Rheumatoid Arthritis (ERA).Objective:To investigate the effect of NeP on the achievement of remission in patients with ERA.Method:The study involved consecutive ERA patients with moderate or high disease activity. The painDETECT Questionnaire (PDQ), the 36-item Short Form Health Survey (SF-36), and the Euro- QoL-5 Dimensions (EQ-5D) were administered to all the patients, and their co-morbidity data were used to calculate their modified Rheumatic Disease Comorbidity Index (mRDCI). After six months’ follow-up, the presence or otherwise of NeP in each individual patient was calculated, and whether or not the Boolean remission criteria were satisfied.Results:The study was completed by 115 patients (76% females) whose PDQ scores indicated that 13% had probable NeP. At the end of the follow-up period, 25 patients (21.7%) met the Boolean remission criteria. Logistic regression analysis showed that baseline PDQ scores (p=0.0023) and the mRDCI (p=0.0054) were the strongest predictors of not being in Boolean remission. Only one of the 15 patients with concomitant NeP achieved Boolean remission.Conclusion:The presence of NeP may affect the achievement of remission in ERA patients. The PDQ can be a useful tool to measure central pain sensitisation in such patients.
An Unusual Presentation of a Rare Scleroderma Mimic: What is Behind the Scenes?
Authors: Ibrahim Rehab Ali , Abdalla Nour El-Hoda Hussien , Shabaan Engy Amr Husssein , Mostafa Noha Bassiouny Hassan 
Published: August 2018

Background:
Scleroderma or systemic sclerosis (SSc) is a rare systemic autoimmune
disease. Many conditions mimic the presentation of SSc, especially skin thickening and fibrosis.
One of these conditions is scleredema, a rare collagen and mucin deposition disorder which was
found to be associated with diabetes mellitus, streptococcal infection or monoclonal gammopathy.

Case Presentation:
A 55 years old female presented with insidious onset and progressive course of
diffuse skin thickening of face, neck, arms, forearms, thighs, chest, back, and excluding both hands
and feet of 6 years’ duration associated with arthralgia, dysphagia and dyspnea on exertion of 1-
year duration. There was no history of Raynaud’s phenomenon. Erythrocyte sedimentation rate was
100 mm/1st h, autoantibodies for SSc were negative, nail fold capillaroscopy normal, pulmonary
function tests showed restrictive pattern and high-resolution computed tomography showed interstitial
lung fibrosis. Patient was not fulfilling the American collage of rheumatology/European League
Against Rheumatism classification criteria for SSc. Skin biopsy was done and revealed histological
appearance of scleredema. Investigations were done for disease association with scleredema. The
patient was not diabetic, antistreptolysin O titer was normal, serum protein electrophoresis, immunofixation
and bone marrow biopsy were done, and the patient was diagnosed as scleredema associated
with immunoglobulin A kappa multiple myeloma. Treatment by combination of bortezomib,
cyclophosphamide, and dexamethasone was started with marked clinical and hematological
improvement.

Conclusion:
Many conditions mimic SSc including scleredema, which may be the initial presentation
of multiple myeloma. Rheumatologists and dermatologists should be able to recognize these
conditions to provide the suitable management and follow-up for these patients.</P>
Androgen Therapy in Male Patients Suffering from Type 2 Diabetes: A Review of Benefits and Risks
Authors: Hassanabad Mortaza F. , Fatehi Mohammad 
Published: August 2018

Background:The current estimated numbers of patients with Type 2 Diabetes (T2D) is believed to be close to 10% of the whole populations of many geographical regions, causing serious concerns over the resulting elevated morbidity and mortality as well as the impact on health care systems around the world. In addition to negatively affecting the quality of life, diabetes is associated with cardiovascular and cerebrovascular complications, indicating that appropriate drug therapy should not only deal with metabolic dysfunction but also protect the vascular system, kidney function and skeletal muscle mass from the effects of the epigenetic changes induced by hyperglycaemia.Objective:To provide an insight into the management of hypogonadism associated with T2D, this review focuses on clinical observations related to androgen therapy in qualified diabetic patients, and discusses the lines of evidence for its benefits and risks. The potential interactions of testosterone with medicines used by patients with T2D will also be discussed.Conclusion:From recent clinical findings, it became evident that a considerable percentage of patients suffering from T2D manifested low serum testosterone and experienced diminished sexual activity, as well as reduced skeletal muscle mass and lower bone density. Although there are some controversies, Testosterone Replacement Therapy (TRT) for this particular population of patients appears to be beneficial overall only if it is implemented carefully and monitored regularly.
Impaired Awareness of Hypoglycaemia in Insulin-treated Type 2 Diabetes Mellitus
Authors: Alkhatatbeh Mohammad J. , Abdalqader Nedaa A. , Alqudah Mohammad A.Y. 
Published: August 2018

Background:
Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia
as an adverse effect of insulin therapy. Hypoglycemia has dangerous consequences that result from
neuroglycopenia and hypersecretion of counter-regulatory hormones. Patients who recognize early
symptoms of hypoglycemia can initiate self-treatment and rectify the situation. Impaired Awareness of
Hypoglycemia (IAH) predisposes patients to severe hypoglycemia and unconsciousness.

Objective:
To assess the prevalence of IAH, the intensity of hypoglycaemic symptoms, the frequency
of severe hypoglycemia and factors associated with IAH in patients with insulin-treated T2DM.

Methods:
This is a cross-sectional study that used Clarke's and Gold's surveys to assess IAH and Edinburgh
survey to assess the intensity of hypoglycemic symptoms in patients with insulin-treated T2DM
(n= 388). The frequency of hypoglycemia and other data were collected by self-reporting or from medical
records.

Results:
The prevalence (95% confidence interval) of IAH was 17.01% (13.27%-20.75%) as determined
by Clarke’s method and 5.93% (3.58-8.28) by Gold’s method (Odds= 3.25, p-value<0.00001).
Drowsiness, hunger, sweating, tiredness, trembling and weakness, were the most intense hypoglycaemic
symptoms, and 6.19% of participants reported at least one episode of severe hypoglycaemia within
the past year. Regardless of classification method used, IAH is not dependent on age, gender, duration
of T2DM or duration of insulin therapy (p-values>0.05). Instead, IAH is positively associated with frequency
of hypoglycaemia during the previous six months (p-value<0.05) and development of severe
hypoglycaemia within the past year (p-value <0.05).

Conclusion:
This study highlights large variability in IAH depending on the method used for assessment.
Increased hypoglycaemia frequency may increase the prevalence of IAH and thus the development
of severe hypoglycemia
Benzophenone Esters and Sulfonates: Synthesis and their Potential as Antiinflammatory Agents
Authors: Arshia  , Jabeen Almas , Faheem Aisha , Khan Khalid M. , Shah Shazia , Perveen Shahnaz 
Published: August 2018

Background:Inflammation is a biological rejoinder of vascular tissues against destructive agents e.g. irritants, damaged cell or pathogens. During inflammation, respiratory burst occurs by activated phagocytes which help to destroy invading pathogens. Phagocytic cells such as neutrophils and macrophages are one of the major sources of reactive oxygen species (ROS) and nitric oxide (NO). Normally, the redox environment is maintained by various antioxidant defense systems, however, these reactive oxygen species may be destructive and can lead to various pathological conditions.Methods:Benzophenone esters and sulfonates (1-18) were synthesized through one pot synthesis by reacting 4-hydroxy benzophenone either different benzoyl chloride or sulfonyl chloride. These synthetic compounds were evaluated for their in vitro immunosuppressive potential on two parameters of innate immune response including inhibition of intracellular reactive oxygen species (ROS) and nitric oxide (NO). ROS were induced in polymorphonuclear leukocytes (PMNs) isolated from human whole blood by serum opsonized zymosan stimulation, whereas NO were produced in J774.2 cells by lipopolysachharides (LPS) stimulation. Moreover, cytotoxicity of compounds was also determined using NIH-3T3 fibroblast cells (ATCC, Manassas, USA) was evaluated by using the standard MTT colorimetric assay.Results:All compounds inhibited the production of ROS at various extent among which compounds 2, 5, 6, 8, 10, 13 and 16 were found to be the potent inhibitors of ROS with IC50 values ranging between (1.0 - 2.2 µg/mL) as compared to ibuprofen (IC50 = 2.5 ± 0.6 µg/mL) as the standard drug. Compounds 2, 7, 11, 13, 14 and 18 showed good inhibition of NO production with % inhibition values ranging between (63.6% - 76.7%) at concentration of 25 µg/mL as compared to NG-monomethyl-Larginine (L-NMMA 65.6 ± 1.1 µg/mL) as the standard. All other derivatives showed moderate to low level of inhibition on both tested parameters. Cytotoxicity activity also showed nontoxicity of synthetic compounds. Structures of all the synthetic compounds were confirmed through 1H-NMR, 13C-NMR, EI-MS and HREI-MS spectroscopic techniques.Conclusion:Compounds 2 and 13 were found to be good dual antiinflammatory (ROS and NO) agent. However, compounds 5, 6, 8, 10 and 16 were found to be selectively active for ROS inhibitory studies. Compounds 7, 11, 14 and 18 were discriminatory active at NO inhibition assay. These initial findings of antiinflammatory activity concluded that these compounds might have the potential to develop a novel non-steroidal antiinflammatory drugs (NSAIDs), non-acidic antiinflammatory agent. Most active compounds 2, 5-8, 10, 13, 14 and 16 showed nontoxicity of synthetic compounds.
Safety of a Clozapine Trial Following Quetiapine-Induced Leukopenia: A Case Report
Authors: Almaghrebi Asma H. 
Published: August 2018

Background:
The clozapine-derivative quetiapine has been shown in some cases to cause leukopenia and neutropenia.

Case Presentation:
We reported on a case of a young female diagnosed with treatment-resistant
schizophrenia. After failed trials of three antipsychotic medications and despite a history of quetiapineinduced
leukopenia, clozapine treatment was introduced due to the severity of the patient’s symptoms,
the limited effective treatment options, and a lack of guidelines on this issue.

Result:
Over a ten-week period of clozapine treatment at 700 mg per day, the patient developed
agranulocytosis. Her white blood cell count sharply dropped to 1.6 &#215; 10<sup>9</sup> L, and her neutrophils
decreased to 0.1 &#215; 10<sup>9</sup> L. There had been no similar reaction to her previous medications
(carbamazepine, risperidone, and haloperidol).

Conclusion:
The safety of clozapine in a patient who has previously experienced leukopenia and
neutropenia with quetiapine requires further investigation. Increased attention should be paid to such
cases. Careful monitoring and slow titration are advisable.
ALDH as a Stem Cell Marker in Solid Tumors
Authors: Toledo-Guzmán Mariel E. , Hernández Miguel Ibañez , Gómez-Gallegos Ángel A. , Ortiz-Sánchez Elizabeth 
Published: August 2018

:Aldehyde dehydrogenase (ALDH) is an enzyme that participates in important cellular mechanisms as aldehyde detoxification and retinoic acid synthesis; moreover, ALDH activity is involved in drug resistance, a characteristic of cancer stem cells (CSCs). Even though ALDH is found in stem cells, CSCs and progenitor cells, this enzyme has been successfully used to identify and isolate cell populations with CSC properties from several tumor origins.:ALDH is allegedly involved in cell differentiation through its product, retinoic acid. However, direct or indirect ALDH inhibition, using specific inhibitors or retinoic acid, has shown a reduction in ALDH activity, along with the loss of stem cell traits, reduction of cell proliferation, invasion, and drug sensitization. For these reasons, ALDH and retinoic acid are promising therapeutic targets.:This review summarizes the current evidence for ALDH as a CSCs marker in solid tumors, as well as current knowledge about the functional roles of ALDH in CSCs. We discuss the controversy of ALDH activity to maintain CSC stemness, or conversely, to promote cell differentiation. Finally, we review the advances in using ALDH inhibitors as anti-cancer drugs.