The Various Roles of PEDF in Cancer.

Pigment epithelium-derived factor (PEDF) is a natural immunomodulator, anti-inflammatory, anti-angiogenic, anti-tumour growth and anti-metastasis factor, which can enhance tumour response to PEDF but can also conversely have pro-cancerous effects. Inflammation is a major cause of cancer, and it has been proven that PEDF has anti-inflammatory properties. PEDF's functional activity can be investigated through measuring metastatic and metabolic biomarkers that will be discussed in this review.

Pilot analysis of intravenous lipid infusion role in COVID-19 mortality.

INTRODUCTION: How to reduce the fatality of coronavirus disease (COVID-19) is still challenging. A proper nutritional support has been always a matter of attention in critically ill patients. MATERIAL AND METHODS: We assessed COVID-19 patients who had received intralipid infusion due to medical indications and compared them with those who did not receive it regarding fatality rate and prognosis. As a part of a data mining project using data of observational cohort of COVID-19 patients hospitalized in the educational centers of Iran University of Medical Sciences, Tehran, Iran, an inferential case series was performed. A total of 19 patients with SARS-CoV-2 infection were selected from the cohort. Briefly, 13 patients survived and 6 patients died, and 12 patients were admitted in intensive care unit (ICU). All dead cases were ICU admitted. The association of intralipid infusion and survival rate was examined using Fisher exact test. No association was observed between intralipid infusion and survival. CONCLUSIONS: No significant protecting effect was observed for patients who received intralipid for medical indications. Since intralipid was administered according to medical indications, surviving of all the non-ICU admitted patients despite having underlying diseases was remarkable. Despite the fact, due to several bias factors that could not be controlled in such a retrospective study, the results might be accidental. We suggest to assess such an effect retrospectively in other centers as well.

Therapeutic potential of pluripotent stem cell-derived dopaminergic progenitors in Parkinson's disease: a systematic review protocol.

BACKGROUND: Parkinson's disease (PD) is the second most common age-dependent neurodegenerative disease that causes motor and cognitive disabilities. This disease is associated with a loss of dopamine content within the putamen, which stems from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Several approved drugs are available that can effectively treat symptoms of PD. However, long-term medical management is often complicated and does not delay or halt disease progression. Alternatively, cell replacement strategies can address these shortcomings and provide dopamine where it is needed. Although using human pluripotent stem cells (hPSCs) for treatment of PD is a promising alternative, no consensus in the literature pertains to efficacy concerns of hPSC-based therapy for PD. This systematic review aims to investigate the efficacy of primate PSC-derived DA progenitor transplantation to treat PD in preclinical studies. METHODS: This is a systematic review of preclinical studies in animal models of PD. We intend to use the following databases as article sources: MEDLINE (via PubMed), Web of Science, and SCOPUS without any restrictions on language or publication status for all related articles published until the end of April 2021. Two independent reviewers will select the titles and abstracts, extract data from qualifying studies, and assess the risk of bias using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Apomorphine-induced rotation test (APO-IR) and amphetamine-induced rotation test (AMP-IR) are defined as the primary outcomes. The standardized mean difference (SMD) by Hedges' g method (r) and odds ratio (OR) and related 95% confidence interval (CI) will be calculated to determine the size effect of the treatment. The heterogeneity between studies will be calculated by "I2 inconsistency of values and Cochran's Q statistical test," where I2 > 50% and/or p < 0.10 suggests high heterogeneity. Meta-analyses of random effects will be run when appropriate. DISCUSSION: This study will present an overview of preclinical research on PSCs and their therapeutic effects in PD animal models. This systematic review will point out the strengths and limitations of studies in the current literature while encouraging the funding of new studies by public health managers and governmental bodies.

An ecological modeling on the adjusted effects of socioeconomic determinants and HLA-DRB1 alleles in fatality of COVID-19 during the early phase of epidemics in a group of countries.

INTRODUCTION: Socioeconomic determinants along with genetic status may affect fatality rate of COVID-19. We intend to investigate the adjusted effects of the HLA-DRB1 alleles and socioeconomic determinants including gross domestic product per capita (GDP cap) and health expenditure per capita (HE cap) in fatality of COVID-19 during the early phase of epidemic in a group of countries. METHODS: As an ecological study, early exposure to epidemics was defined as having more than 5000 confirmed cases of COVID-19 from 1 March 2020 to 1 April 2020. Poisson regression was used to report adjusted incidence rate ratio (IRR) for case fatality rate in this constant time period. RESULTS: Fourteen countries were eligible. Among the alleles, DR7 showed the strongest risk factor (IRR=112.535, P<0.001). Having GDP cap more than 40000$ or having HE cap more than 3000$ was a protecting factor (IRR=0.899, P<0.001, adjusted with allele DR7). Having GDP cap more than 40000$ along with having HE cap more than 3000$ was a protecting factor (IRR=0.471, P<0.001, adjusted with allele DR7). CONCLUSION: Socioeconomic status of the countries may compensate the probable harmful effect of some HLA-DRB1 alleles. This conclusion was limited to a period that all the selected countries had almost similar governmental intervention.

Ultrasensitive Detection of Plasma Amyloid-ß as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer's Disease.

BACKGROUND: Aberrant amyloid-ß (Aß) deposition in the brain occurs two decades prior to the manifestation of Alzheimer's disease (AD) clinical symptoms and therefore brain Aß load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain Aß deposition, attractive candidates for investigation as surrogate markers. OBJECTIVE: Investigation of plasma Aß as a surrogate marker for brain Aß deposition in cognitively normal elderly individuals. METHODS: Plasma Aß40 and Aß42 concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain Aß deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer 18F-Florbetaben, plasma Aß was compared between 32 participants assessed to have low brain Aß load (Aß-, SUVR <1.35) and 63 assessed to have high brain Aß load (Aß+, SUVR ≥1.35). RESULTS: Plasma Aß42/Aß40 ratios were lower in the Aß+ group compared to the Aß-group. Plasma Aß40 and Aß42 levels were not significantly different between Aß-and Aß+ groups, although a trend of higher plasma Aß40 was observed in the Aß+ group. Additionally, plasma Aß42/Aß40 ratios along with the known AD risk factors, age and APOEɛ4 status, resulted in Aß+ participants being distinguished from Aß-participants based on an area under the receiver operating characteristic curve shown to be 78%. CONCLUSION: Plasma Aß ratios in this study are a potential biomarker for brain Aß deposition and therefore, for preclinical AD. However, this method to measure plasma Aß needs further development to increase the accuracy of this promising AD blood biomarker.

Characterization of a new member of kunitz-type protein family from the venom of Persian false-horned viper, Pseudocerastes persicus.

A new member of kunitz-type protein family, PPTI (PseudocerastesPersicusTrypsin Inhibitor), was isolated from the venom of Persian false horned viper Pseudocerastes persicus and characterized. Mass spectrometry and amino acid sequencing revealed that PPTI is a 68 amino acid protein with molecular weight of about 7.6 kDa. The first amino acid residue of PPTI is N-terminally blocked via a post translational modification to pyroglutamyl. Sequence comparison against UniProtKB shows a high sequence similarity of PPTI with kunitz-type proteins, especially serine protease inhibitors and dendrotoxins (DTXs). The number of cysteines and disulfide bonding pattern of PPTI are the same as kunitz-type proteins. Based on sequence derive information, anti-protease activity of PPTI against trypsin was experimentally examined. The constructed homology models of PPTI confirmed the ability of PPTI to fold similarly to kunitz domain. The presence of characteristic basic-hydrophobic functional dyad of DTXs in PPTI supports its inhibitory potential against potassium channels. In summary, this study hypothesized the dual functionality of PPTI according to its inhibitory effect on trypsin and its potential ability in blocking potassium channel.

Selective cyclooxygenase-2 inhibitor compound 11b improves haloperidol-induced catatonia by enhancing the striatum dopaminergic neurotransmission.

The aim of this research was to investigate the Cyclooxygenase-2 (COX-2) selective inhibition effect on haloperidol-induced catatonia. In this study, the effect of orally, acutely and Sub-chronically administrations of compound 11b [1-(phenyl)-5-(4-methylsulfonylphenyl)-2-ethylthioimidazole] (2, 4 and 8 mg/kg), a newly selective COX-2 inhibitor, was investigated against the haloperidol-induced catatonia phenomenon comparing to the standard drug scopolamine (1 mg/Kg) followed by microdialysis analysis of Striatum dopaminergic neurotransmission. The results showed a great potency for compound 11b in improvement of catalepsy followed by enhancing the dopaminergic neurotransmission p < 0.05. In addition, our statistical analysis showed that the protective effect of compound 11b against haloperidol-induced catatonia was both dose- and time-dependent. These findings are additional pharmacological data that suggest the effectiveness of compound 11b in treatment of schizophrenic drug overdoses and also Parkinson's disease (PD) affiliated rigidity.

The selective cyclooxygenase-2 inhibitor, the compound 11b improves haloperidol induced catatonia by enhancing the striatum dopaminergic neurotransmission.

A substantial amount of evidence has proposed an important role for Cyclooxygenase-2 (COX-2) enzyme in brain diseases and affiliate disorders. The purpose of this research was studying the effects of COX-2 selective inhibition on haloperidol-induced catatonia in an animal model of drug overdose and Parkinson's disease (PD). In this study, the effect of acute and Sub-chronic oral administration of a new selective COX-2 inhibitor, i.e. the compound 11b or 1-(Phenyl)-5-(4-methylsulfonylphenyl)-2-ethylthioimidazole, in a dosage of 2, 4 and 8 mg/kg on haloperidol-induced catatonia was evaluated and compared to the standard drug scopolamine (1 mg/kg) by microanalysis of Striatum dopaminergic neurotransmission. The results showed a very high potency for 11b in improving the catalepsy by enhancing the dopaminergic neurotranmission (p < 0.05). In addition, statistical analysis showed the dose- and time-dependent behavior of the observed protective effect of 11b against the haloperidol-induced catatonia and enhancement of the dopaminergic neurotransmission. These findings are additional pharmacological data that suggest the effectiveness of COX-2 inhibition in treatment of schizophreny-associated rigidity.

Ciprofloxacin: a novel therapeutic agent for iron overload?

OBJECTIVE: Major thalassemia is one of the hematological diseases requiring multiple blood transfusions, which results in iron overload in the liver, heart and other organs. Current iron chelation therapy consists of intravenous (IV) deferoxamine and oral deferasirox and deferiprone. Although these chelators are effective, many side effects are reported. In the present study, the iron-chelating effect of ciprofloxacin with good oral absorption was investigated. METHODS: Thirty male albino Wistar rats were used for the study. Ciprofloxacin (7 or 14 mg/kg per day) was administered simultaneously with iron (0.03 g/kg per day) or after one-month administration of iron. Ciprofloxacin effect on iron absorption in the liver and heart was studied carefully using atomic absorption. RESULTS: A significant decrease in the liver and heart iron following the ciprofloxacin (14 mg/kg per day) administration was observed, when compared with the control group. This ciprofloxacin-induced tissue iron depletion was more pronounced when it was administered simultaneously with iron, when it was administered for a longer duration (2 months rather than 1 month) and when it was given in higher doses (14 mg/kg per day). CONCLUSION: Administration of ciprofloxacin may help to decrease the burden of parenteral administration, thereby improving compliance and also the life expectancy of thalassemic patients.