Discovery of a biomarker for ß-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction - Parallel Ion Parking.

ß-thalassemia is a quantitative hemoglobin (Hb) disorder resulting in reduced production of Hb A and increased levels of Hb A2. Diagnosis of ß-thalassemia can be problematic when combined with other structural Hb variants, so that the separation approaches in routine clinical centers are not sufficiently decisive to obtain accurate results. Here, we separate the intact Hb subunits by high-performance liquid chromatography, followed by top-down tandem mass spectrometry of intact subunits to distinguish Hb variants. Proton transfer reaction-parallel ion parking (PTR-PIP), in which a radical anion removes protons from multiply charged precursor ions and produces charge-reduced ions spanning a limited m/z range, was used to increase the signal-to-noise ratio of the subunits of interest. We demonstrate that the δ/ß ratio can act as a biomarker to identify ß-thalassemia in normal electrospray ionization MS1 and PTR-PIP MS1. The application of PTR-PIP significantly increases the sensitivity and specificity of the HPLC-MS method to identify δ/ß ratio as a thalassemia biomarker.

Impaired oxygen extraction and adaptation of intracellular energy metabolism in cerebral small vessel disease.

Background: We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative T 2 ' mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD). Materials and methods: 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional 31P MRSI and oxygenation-sensitive quantitative T 2 ' mapping (1/ T 2 '  = 1/T2* - 1/T2) at 3 Tesla (T). PHi was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative T 2 ' values were averaged across the entire white matter (WM). Furthermore, T 2 ' values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls. Results: Quantitative T 2 ' values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51 ± 16.94 vs. 138.19 ± 12.66 ms and 147.45 ± 18.14 vs. 137.99 ± 12.19 ms, p < 0.05). WM T 2 ' values correlated significantly with the WMH load (ρ=0.441, p = 0.006). Increased T 2 ' was significantly associated with more alkaline pHi (ρ=0.299, p < 0.05). Both T 2 ' and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p = 0.001 and ρ=0.452, p = 0.016). Conclusions: This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.

Conservative endovascular management for intractable delayed hemorrhage after laparoscopic-assisted vaginal hysterectomy: Two case reports.

Delayed hemorrhage from the vaginal stump is a rare complication following hysterectomy. Most cases can be managed by vaginal packing with or without vaginal vault suturing. However, where such initial management fails, the condition is potentially life-threatening and requires immediate intervention. We report two cases successfully managed with transcatheter arterial embolization (TAE). First, a 38-year-old woman presented with lower abdominal pain 12 days after laparoscopic-assisted vaginal hysterectomy (LAVH) for a uterine myoma. Oral antibiotics were administered for pelvic infection. Two days later, she experienced increased bleeding. After failing to achieve hemostasis with vaginal vault suturing, computed tomographic angiography showed extravasation from a pseudoaneurysm in the peripheral branch of the left uterine artery. Hemostasis was achieved with TAE. Second, a 40-year-old woman presented with fever and increased abdominal pain 6 days after LAVH for severe dysplasia of the uterine cervix. Intravenous antibiotics were administered for pelvic infection. Twenty-one days after LAVH, she experienced increased bleeding. Computed tomographic angiography showed extravasation from a peripheral thin branch of the right uterine artery. Temporary hemostasis was achieved with vaginal vault suturing; however, bleeding recommenced 12 h later. Hemostasis was achieved with TAE. We conclude that endovascular management is a feasible option for intractable delayed hemorrhage after hysterectomy, when vaginal vault suturing fails to achieve hemostasis.

Spontaneous acute forearm compartment syndrome: Case report of a clinical diagnosis with limited imaging options.

Diagnostic radiology is essential for providing targeted management of different diseases. Thus, there has been a dramatic increase in the demand for medical imaging. However, acute compartment syndrome (ACS) is one of the clinical scenarios in which radiology has limited value. The authors report a nontraumatic spontaneous ACS in the forearm of a 56-year-old female. The roles of Ultrasound and MRI, if available, are also illustrated. Limited reports of spontaneous ACS are published in the literature; we hope this case adds to the limited data. Our goal in reporting this case is to improve clinical practice with favorable outcomes for the patients involved globally by alert to the onset of ACS to promote early detection and timely fasciotomy. Also, we aim to increase awareness among physicians and radiologists of the limitations of radiology in specific clinical scenarios. Finally, it may aid in illuminating a possible link between malignant hypertension, spontaneous bleeding/hematoma, and ACS.

Efficacy of steroid pulse therapy for miliary tuberculosis complicated by acute respiratory distress syndrome.

Introduction: Acute respiratory distress syndrome (ARDS) is considered a poor prognostic factor for miliary tuberculosis (MTB), but little is known about the effectiveness of steroid pulse therapy for MTB complicated by ARDS. Patients and methods: Medical records were used to retrospectively investigate the prognosis and clinical information of 13 patients diagnosed with MTB complicated by ARDS among 68 patients diagnosed with MTB at our hospital between January 1994 and October 2016. None of the patients had multidrug resistant tuberculosis (TB). MTB was diagnosed by 1 radiologist and 2 respiratory physicians based on the observation of randomly distributed, uniformly sized diffuse bilateral nodules on chest computed tomography and the detection of mycobacterium TB from clinical specimens. ARDS was diagnosed based on the Berlin definition of ARDS. The effect of steroid pulse therapy on death within 3 months of hospitalization was examined using Cox proportional hazards models. Variables were selected by the stepwise method (variable reduction method). Results: Six of 8 patients with MTB complicated by ARDS were alive 3 months after hospitalization in the steroid pulse therapy group, whereas only 1 of 5 patients was alive in the non-steroid pulse therapy group. Analysis of factors related to the survival of patients with MTB complicated by ARDS revealed that steroid pulse therapy was the strong prognostic factor (hazard ratio = 0.136 (95 % CI: 0.023-0.815)). Conclusion: Our findings suggest that steroid pulse therapy improves the short-term prognosis of patients with MTB complicated by ARDS.

Latent class analysis: an innovative approach for identification of clinical and laboratory markers of disease severity among COVID-19 patients admitted to the intensive care unit.

Objective: The aim of this study was to identify clinical and laboratory phenotype distribution patterns and their usefulness as prognostic markers in COVID-19 patients admitted to the intensive care unit (ICU) at Tygerberg Hospital, Cape Town. Methods and results: A latent class analysis (LCA) model was applied in a prospective, observational cohort study. Data from 343 COVID-19 patients were analysed. Two distinct phenotypes (1 and 2) were identified, comprising 68.46% and 31.54% of patients, respectively. The phenotype 2 patients were characterized by increased coagulopathy markers (D-dimer, median value 1.73 ng/L vs 0.94 ng/L; p < 0.001), end-organ dysfunction (creatinine, median value 79 µmol/L vs 69.5 µmol/L; p < 0.003), under-perfusion markers (lactate, median value 1.60 mmol/L vs 1.20 mmol/L; p < 0.001), abnormal cardiac function markers (median N-terminal pro-brain natriuretic peptide (NT-proBNP) 314 pg/ml vs 63.5 pg/ml; p < 0.001 and median high-sensitivity cardiac troponin (Hs-TropT) 39 ng/L vs 12 ng/L; p < 0.001), and acute inflammatory syndrome (median neutrophil-to-lymphocyte ratio 15.08 vs 8.68; p < 0.001 and median monocyte value 0.68 × 109/L vs 0.45 × 109/L; p < 0.001). Conclusion: The identification of COVID-19 phenotypes and sub-phenotypes in ICU patients could help as a prognostic marker in the day-to-day management of COVID-19 patients admitted to the ICU.

Plasma-induced nanoparticle aggregation for stratifying COVID-19 patients according to disease severity.

Stratifying patients according to disease severity has been a major hurdle during the COVID-19 pandemic. This usually requires evaluating the levels of several biomarkers, which may be cumbersome when rapid decisions are required. In this manuscript we show that a single nanoparticle aggregation test can be used to distinguish patients that require intensive care from those that have already been discharged from the intensive care unit (ICU). It consists of diluting a platelet-free plasma sample and then adding gold nanoparticles. The nanoparticles aggregate to a larger extent when the samples are obtained from a patient in the ICU. This changes the color of the colloidal suspension, which can be evaluated by measuring the pixel intensity of a photograph. Although the exact factor or combination of factors behind the different aggregation behavior is unknown, control experiments demonstrate that the presence of proteins in the samples is crucial for the test to work. Principal component analysis demonstrates that the test result is highly correlated to biomarkers of prognosis and inflammation that are commonly used to evaluate the severity of COVID-19 patients. The results shown here pave the way to develop nanoparticle aggregation assays that classify COVID-19 patients according to disease severity, which could be useful to de-escalate care safely and make a better use of hospital resources.

Toxic effects of excess exposure to boric acid on serum biochemical aspect, hematology and histological alterations and ameliorative potential role of melatonin in rats.

The current work clarifies the negative effects of excess exposure to boric acid (H3BO3) as a boron-containing compound on rats and the possible ameliorative effect of melatonin (MEL). Forty rats were equally divided into 5 groups as follows: group 1 was treated as control while groups 2, 3, 4 and 5 were orally administered corn oil (0.5 ml), H3BO3 (1330 mg/kg BW), MEL (10 mg/kg BW) and H3BO3 + MEL for 28 consecutive days, respectively. At the end of the experiment, blood was sampled for biochemical and hematological analysis and tissues were collected for histopathological examination. The obtained results demonstrated that the exposure to H3BO3 induced hepatorenal dysfunctions, alterations in bone-related minerals and hormones levels, prostaglandin E2 as inflammatory mediator and hematological indices. H3BO3 induced histological alterations in the liver, kidneys, bone and skin. The co-administration of MEL with H3BO3 resulted in a significant improvement in most of the measured parameters and restoration of morpho-functional state of different organs compared to the H3BO3 group. In conclusion, the study clearly demonstrated that H3BO3- induced various adverse effects and that melatonin may be beneficial in a partial mitigating the H3BO3 and may represent a novel approach in the counteracting its toxicity.

Haptoglobin polymorphism affects its N-glycosylation pattern in serum.

Introduction: Haptoglobin (Hp) is an abundant acute-phase protein secreted mainly by the liver into the bloodstream. There are three Hp protein phenotypes (Hp type 1-1, 2-1, and 2-2), which differ in the number of α- and ß-chains, type of α-chain (the ß-chain type remains the same in all the Hp phenotypes), and the polymers that they form via disulfide bonds. Hp has four N-glycosylation sites on the ß-chain. Glycosylation of Hp has been reported frequently as a potential glycobiomarker for many diseases; however, whether Hp polymorphism affects its glycosylation has not yet been addressed extensively or in depth. Objectives: This study investigated the differences between the glycosylation patterns of Hp phenotypes using serum from 12 healthy individuals (four for each Hp phenotype). Method: An efficient method for isolating Hp from serum was established and subsequently the Hp phenotype of each sample was characterized by immunoblotting. Then, LC-MS/MS analysis of isolated Hp after treatment with three exoglycosidases (sialidase, α2-3 neuraminidase, Endo F3) was performed to characterize the glycosylation pattern of Hp for each individual sample. Results: The data reveal significant differences among the branching, sialylation, and fucosylation of Hp types, documenting the effect of Hp polymorphism on its glycosylation. Conclusion: Overall, the study suggests that Hp phenotype characterization should be considered during the investigation of Hp glycosylation.

Effect of a diet based on Iranian traditional medicine on inflammatory markers and clinical outcomes in COVID-19 patients: A double-blind, randomized, controlled trial.

Introduction: SARS-CoV-2 causes severe acute respiratory syndrome prompting worldwide demand for new antiviral treatments and supportive care for organ failure caused by this life-threatening virus. This study aimed to help develop a new Traditional Persian Medicine (TPM) -based drug and assess its efficacy and safety in COVID-19 patients with major symptoms. Methods: In February 2022, a randomized clinical trial was conducted among 160 patients with a confirmed diagnosis of COVID-19 admitted to Emam Reza (AJA) Hospital in Tehran, Iran. During their hospitalization, the intervention group received a treatment protocol approved by Iran's Ministry of Health and Medical Education (MOHME), consisting of an Iranian regimen, Ficus carica; Vitis vinifera, Safflower, Cicer arietinum, Descurainiasophia seeds, Ziziphus jujuba, chicken soup, barley soup, rose water, saffron, and cinnamon spices. All patients were compared in terms of demographics, clinical, and laboratory variables. Results: One hundred and sixty COVID-19 patients were divided into two groups: intervention and control. In baseline characteristics, there was no significant difference between the intervention and control groups (p>0.05). Using SPSS software version 22, statistical analysis revealed a significant difference in four symptoms: myalgia, weakness, headache, and cough (p<0.05). During the 5-day treatment period, the control group had significantly lower C-reactive protein (p<0.05). Conclusion: While more research with a larger sample size is needed, the proposed combination appears to be effective in the treatment of symptoms as well as inflammatory biomarkers such as C-reactive protein in COVID-19 patients.Iranian registry of clinical trials (IRCT) IRCT20220227054140N1.

Association between thrombocytopenia and the severity of Covid-19 infection among hospitalized Egyptian patients.

Background: COVID-19, which is caused by the corona virus 2 that causes severe acute respiratory syndrome, causes a respiratory and systemic illness that in 10-15% of patients escalates to a severe form of pneumonia. Thrombocytopenia is frequent in patients with COVID-19. We aimed to evaluate the association between thrombocytopenia and the severity of COVID-19 infection in hospitalized patients. Methods: A cross-sectional study was done on 800 Egyptian patients with confirmed covid-19 infection. They were divided into Group I (Mild): 200 symptomatic patients meeting the case definition for COVID-19 without radiological evidence of pneumonia or hypoxia. Group II (Moderate): 200 patients with clinical signs of non-severe pneumonia and radiological evidence of pneumonia. Group III (Severe): 200 patients with clinical signs of pneumonia plus: respiratory or lung dysfunction. Group IV: 200 critically ill patient in ICU: Acute respiratory distress syndrome (ARDS).Results: there was a highly statistically significant difference between the studied groups regarding thrombocytopenia (p < 0.001). Thrombocytopenia was statistically higher in severe and critically ill patients. In addition, a statistically significant difference found in outcome among the studied groups (p < 0.05) {critically ill (40%), severe (17.5%)}. The most common cause of death was respiratory failure, which occurred in 28 severe patients (80%) and 65 critically ill patients (81.25%), followed by hemorrhage due to thrombocytopenia, which occurred in 7 severe patients (20%) and 15 critically ill patients, respectively (18.75%). Conclusion: The Platelet count is a straightforward, inexpensive, as well as easily available laboratory parameter that is frequently linked to severe covid-19 infection and a significant death risk.

Volume-controlled ventilation versus pressure-controlled ventilation during spine surgery in the prone position: A meta-analysis.

Background: Many studies have investigated a comparison of the potency and safety of PCV versus VCV modes in spinal surgery in prone position. However, controversy about the maximal benefits of which ventilation modes remains. The main purpose of this meta-analysis was to investigate which one is the optimal ventilation for surgery patients undergoing spine surgery in prone position between the two ventilation modes as PCV and VCV. Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, the Cochrane Library, and Google Scholar for potentially eligible articles. The continuous outcomes were analyzed using the mean difference and the associated 95% confidence interval. Meta-analysis was performed using Review Manager 5.4 software. Results: Our meta-analysis included 8 RCTs involving a total of 454 patients between 2012 and 2020. The results demonstrated that IOB, Ppeak and CVP for VCV are significantly superior to PCV in spinal surgery in prone position. And PCV had higher Cdyn and PaO2/FiO2 than VCV. But there was no significant difference between PCV and VCV in terms of POB, Hb, HCT, HR and MAP. Conclusions: The PCV mode displayed a more satisfying effect than VCV mode. Compared to VCV mode in same preset of tidal volume, the patients with PCV mode in prone position demonstrated less IOB, lower Ppeak and CVP, and higher PaO2/FiO2 in spinal surgery. However, there is no obvious difference between PCV and VCV in terms of hemodynamics variables (HR and MAP).

Clinical interpretation of serum hepcidin-25 in inflammation and renal dysfunction.

Introduction: Hepcidin is a hormone that regulates systemic iron homeostasis. Serum hepcidin levels are under the influence of various stimuli, particularly inflammation and renal dysfunction. The measurement of hepcidin in circulation is a potentially useful clinical tool in the diagnosis, monitoring and treatment of iron metabolism disorder, although clinical interpretation of hepcidin level remains difficult. We evaluated he diagnostic potential and limitations of hepcidin-25 by investigating its relationship with iron and hematological indices, inflammation, and renal dysfunction. Methods: This retrospective study included 220 adult patients not requiring dialysis. Variations of biologically active hepcidin-25 were examined using a mass spectrometry-based assay in various inflammatory and renal states. The log[hepcidin]:log[ferritin] ratio was calculated as an hepcidin index. Results: In 220 adult patients not requiring dialysis, variation in hepcidin-25 level was significantly larger once CRP exceeded 10 mg/l (p < 0.001). Inflammation was not a determinant of hepcidin-25 in the setting of renal dysfunction. Hepcidin-25 median (7.37 nM) and variance were significantly higher (p < 0.001), once estimated glomerular filtration rate (eGFR) dropped below 30 ml/min/1.73 m2. The log[hepcidin]:log[ferritin] index normalized hepcidin levels. Patients with iron deficiency have a notably lower index when compared to controls (-0.66 vs 0.3). Conclusion: Severe renal dysfunction (eGFR < 30) affected hepcidin-25 expression and clearance to variable degree between individuals. Although, hepcidin-25 testing is not warranted in patients with infection, inflammatory autoimmune conditions (CRP > 10 mg/l) and/or severe renal dysfunction (eGFR < 30), the hepcidin index may serve as a potential biomarker for iron deficiency in complex cases.

Does Raised Transaminases Predict Severity and Mortality in Patients with COVID 19?

Background: The most dreaded pandemic grappling world now, the Coronavirus Disease 2019 (COVID-19), chiefly involves the respiratory system; nevertheless, it is a multisystem disorder. Its involvement of the hepatic system is considerable; however, still emerging are its clinical implications and the effects on morbidity and mortality. Aim: The aim of this study is to report on the various aspects of its hepatic involvement by describing the alterations in tests of liver function and its significance in the disease outcome in a cohort of hospitalized COVID-19 patients at a tertiary center in northern India. Methods: This is a retrospective cohort study conducted in a tertiary-care hospital in northern India. All confirmed hospitalized COVID-19 cases aged 15 and above from Apr to Oct 2020 with no pre-existing liver disease were included. The primary endpoint was death at 28 days. Statistical analysis included descriptive analysis, sensitivity-specificity, and univariable and multivariable regression analysis as well as survival analysis. Results: A total of 708 patients with COVID-19 fulfilled the inclusion criteria included 561 (79.2%) males and 147 (20.8%) females. The median age was 49 (IQR = 25) years. Mild and moderate/severe disease were seen in 508 (71.8%) and 200 (28.2) patients, respectively. Serum bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were elevated in 6.92%, 69.91%, and 80.22% of patients, respectively. In univariable logistic regression, AST [odds ratio; OR 1.008 95% CI (1.005-1.012) per 1 IU/L increase] and ALT [OR 1.005 95% CI (1.002-1.007) per 1 IU/L increase] were significantly associated with the odds of moderate to severe disease but only AST was significant after adjustment to age, sex, and comorbidity [adjusted odds ratio; aOR 1.007 95% CI (1.003-1.011) per 1 IU/L increase]. Serum albumin was negatively associated with the odds of moderate to severe disease and remained significant in the adjusted model [aOR 0.217 95%CI (0.149-0.316) per 1 g/dL increase].Ninety-six patients succumbed to illness [case fatality rate; CFR 13.6%). In adjusted Cox Proportional-Hazards Model for mortality, AST [adjusted hazard ratio; aHR 1.002 95% CI (1.000-1.003) per 1 IU/L increase] and serum albumin [aHR 0.396 95% CI (0.285-0.549) per 1 g/dL increase] showed significant association with mortality. Conclusion: Liver function abnormalities are common in patients with COVID-19. In particular, AST and serum albumin levels are effective predictors of disease severity and mortality and can be used as markers of fatal disease in the management as well as prognostication of COVID-19.

Surgical Procedures in Patients Awaiting Liver Transplantation: Complications and Impact on the Liver Function.

BACKGROUND: Potential indications for surgery frequently arise in patients awaiting liver transplantation. There is a risk of hepatic decompensation and death triggered by surgical trauma, but this has not been studied in detail in this unique population. We aimed to quantify the impact of surgical interventions in patients awaiting liver transplantation on hepatic function and identify risk factors for decompensation. METHODS: All surgeries between 2000 and 2018 in patients awaiting liver transplantation in a highvolume German liver transplant center were analyzed retrospectively. Change in liver function measured as indicated by MELD score was assessed and complication rates recorded. The primary endpoint was a composite of an increase in MELD score by > 5 points or death. A logistic regression model was used for multivariate analysis to identify risk factors. RESULTS: In total, 177 surgical procedures in 148 patients were analyzed. The primary endpoint was reached in 42 cases (23.7%). The overall in-hospital complication rate (including death) was 44.1%. Multivariate analysis identified elevated leukocyte count, perioperative blood transfusion, preoperative presence of ascites, and preoperative circulatory support as independent risk factors for a decline in liver function or death. CONCLUSION: Surgery in patients awaiting liver transplantation carries a relevant risk of hepatic decompensation and death that needs to be considered when deciding whether to perform elective surgery prior to or defer until after liver transplantation.

A Rare Case of Addison's Disease Presenting With Intermittent Pancytopenia and Cardiac Tamponade.

OBJECTIVE: To report the first case, to our knowledge, of intermittent pancytopenia and cardiac tamponade occurring together in association with Autoimmune Addison's Disease (AAD). METHODS: A 21 year-old woman presented on three different occasions with multiple complaints. Her evaluation was significant for intermittent pancytopenia (white blood cell, 1.3-3.0 × 103/µL [normal 4.5-11 × 103]; hemoglobin, 8.8-9.6 g/dL [11-16]; and platelets, 102-117 × 103/µL [150-400 × 103/µL]) and pericardial effusion with cardiac tamponade. Further investigation including a morning serum cortisol level of 0.6 µg/dL (5.27-22.45 µg/dL), adrenocorticotropic hormone level of 1027 pg/mL (normal 6-50 pg/mL), and positive 21-hydroxylase antibodies confirmed the diagnosis of primary adrenal insufficiency due to AAD. Treatment with steroids resulted in prompt hemodynamic recovery with normalization of all blood cell lines. RESULTS: The diagnosis of AAD is often delayed or overlooked. Pancytopenia occurring in AAD is most likely due to either marrow suppression in the setting of acute illness and exacerbated by hypoadrenalism or possibly an autoimmune-mediated marrow reaction. Pericarditis with cardiac tamponade has been described in AAD occurring in the setting of polyglandular autoimmune syndrome type II. The pathogenesis involves autoimmune inflammation of the pericardium, which precipitates an acute inflammatory reaction and rapid fluid accumulation. CONCLUSION: Pericarditis with cardiac tamponade and intermittent neutropenia may be rare manifestations of an Addisonian crisis.

Wound healing activity of the hydroethanolic extract of the leaves of Maytenus ilicifolia Mart. Ex Reis.

BACKGROUND AND AIM: Maytenus ilicifolia has analgesic, healing, antioxidant and anti-inflammatory properties. This study evaluated effect of the hydroalcoholic extract of M. ilicifolia leaves on skin wound repair. EXPERIMENTAL PROCEDURE: Wounds were induced on mice and treated with the extract. The treatment was performed daily, until day 7 after wound induction. Wound closure was measured and the features of the repaired tissue were investigated, including mast cell quantification, neutrophil and macrophage activities, collagen deposition, angiogenesis, and pro-metalloproteases and metalloproteases 2 and 9 activity (pro-MMPs and MMPs). RESULTS AND CONCLUSION: The M. ilicifolia extract accelerated the closure of wounds. The extract at a concentration of 4% was found to be effective, presenting anti-inflammatory effects and hemoglobin increased, along with increased soluble, total and type III collagens in the wound. In addition, there was an increase in pro-MMP9 and MMP9 activity after day 7th of treatment. The phenolic compounds and tannins present in this plant could be associated with the anti-inflammatory and healing activities observed in this study. Therefore, the ability to modulate essential parameters for accelerated and adequate healing as shown here suggests that the use of standardised extracts of M. ilicifolia and its fractions enriched in polyphenols may represent a therapeutic strategy for the treatment of wounds.

Recent advances in nanomedicines for the treatment of ischemic stroke.

Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the brain. Ischemia would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain, where the ischemic cascade eventually leads to cell death and brain infarction. Extensive researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic stroke. However, traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment efficacy. Nanomedicine provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo, achieve effective drug accumulation at the target site, enhance the therapeutic effect and meanwhile reduce the side effect. In this review, we comprehensively describe the pathophysiology of stroke, traditional treatment strategies and emerging nanomedicines, summarize the barriers and methods for transporting nanomedicine to the lesions, and illustrate the latest progress of nanomedicine in treating ischemic stroke, with a view to providing a new feasible path for the treatment of cerebral ischemia.

In vivo and in silico studies of Dennettia tripetala essential oil reveal the potential harmful effects of habitual consumption of the plant seed.

Dennettia tripetala G. Baker (Annonaceae), is a plant with nutritional, social economy, and medicinal values. Its rising medicinal profile makes this plant a prospect in drug discovery. However, the reported strong addictive potential among habitual consumers makes the need to establish its safety imperative. In this report, we evaluated the safety profile of the essential oil of the seed of D. tripetala (EODS) in nulliparous female Wistar rats using in vivo single and repeated dose toxicity profiling, as well as in silico toxicity profiling of its known seed oil derived phytoconstituents. Our results showed consistent significant dose-dependent alterations in relative body weights, organ-body and organ-brain weight ratios, haematological and biochemical indices, as well as liver and kidney histoarchitectures, following single and repeated oral administrations. Significant alterations in liver and kidney histoarchitectures were consistent with the observed significant increase in AST/ALT ratio, suggesting deleterious effects of EODS on the kidney and liver. However, the lack of alterations in the histoarchitectures of the hippocampus and hypothalamus suggests that the brain may not have been adversely affected. Also, the in silico analysis suggests that hepatotoxic effects of EODS may be linked to Benzylnitrile, Humulene, Linalool, (Z)-ß-Ocimene. In addition, the failure of ß-Phenylnitroethane, the most abundant phytoconstituent of EODS, to pass phases I and II in silico toxicity screening, and the presence of Caryophyllene oxide, a known toxic compound, coupled with the predicted binding of both to DNA and protein, low LD50 and high percent mortality at 250 mg/kg of repeated doses, further confirmed the potentially toxic nature of EODS. We concluded that based on our in vivo and in silico observations, there is an urgent need for public education to regulate the excessive consumption of the seeds of D. tripetala.