Cardioprotective, hypotensive and toxicological studies of Populus ciliata (Wall. ex Royle).

Populus ciliata Wall ex. Royle has folkloric repute to treat various cardiovascular ailments and related disorders. The current study was designed to evaluate the toxic profile, cardioprotective and hypotensive effects of Populus ciliata (Wall. ex Royle). Populus ciliata crude ethanolic extract (Pc. Cr) and its aqueous (Pc. Aq) & organic (Pc. Dcm) fractions were tested on isolated aorta of rat and rabbit having intact and non-intact endothelium respectively. Pc. Cr & Pc. Aq relaxed the contractions induced by PE (1 µM)-induced and K+ (80 mM)-induced on aorta, possibly by mediating endothelium derived relaxing factor (EDRF) in intact endothelium and voltage dependent L-type calcium channels blocking (CCB) mechanism in non-intact endothelium. Pc. Cr showed anti-hypertensive & cardioprotective activity by decreasing force of contraction & heart rate on isolated rabbit paired atria and reduced blood pressure in anesthetized rat. Cardioprotective effect of Pc. Cr was assessed in isoproterenol induced acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) in Sprague Dawley rats. In LVH, Pc. Cr exerted positive effects by decreasing angiotensin II & renin and increasing cGMP & nitric oxide (NO) with reduced cardiac fibrosis, necrosis and cardiac cell size. In AMI, Pc. Cr responded effectively by decreasing cardiac markers creatinine kinase (CK), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LD) in blood associated with less edema and necrosis. Presence of catechin, vinallic acid, P-coumeric acid and quercitin identified through HPLC support the effectiveness of Pc. Cr in hypertension, AMI and LVH. Pc. Cr showed no significant adverse effects in Sprague Dawley albino rats after acute & sub-acute treatment in histopathological investigation. Extract of Populus ciliata showed vasorelaxant, hypotensive and cardioprotective effect in Sprague Dawley albino rats and white albino rabbit by mediating EDRF and voltage dependent L-type CCB mechanism respectively.

Podophyllotoxin: History, Recent Advances and Future Prospects.

Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is the frontline chemotherapeutic drug used against various cancers due to its superior anticancer activity. It has recently been redeveloped for the purpose of treating cytokine storm in COVID-19 patients. Podophyllotoxin and its naturally occurring congeners have low bioavailability and almost all these initially discovered compounds cause systemic toxicity and development of drug resistance. Moreover, the production of synthetic derivatives that could suffice for the clinical limitations of these naturally occurring compounds is not economically feasible. These challenges demanded continuous devotions towards improving the druggability of these drugs and continue to seek structure-optimization strategies. The discovery of renewable sources including microbial origin for podophyllotoxin is another possible approach. This review focuses on the exigency of innovation and research required in the global R&D and pharmaceutical industry for podophyllotoxin and related compounds based on recent scientific findings and market predictions.

Pharmacological and Therapeutic Properties of Punica granatum Phytochemicals: Possible Roles in Breast Cancer.

Background: Pomgranate (Punica granatum) represents a high source of polyphenols with great bioavailability. The role of this fruit in the prevention and treatment of various malignant pathologies has been long time cited in both scientific and non-scientific literature, making thus important to identify its involvement in the pathophysiological processes. The treatment for breast cancer had focused on the inhibition of the mechanisms that governs the estrogen activity. These mechanisms are covered either by the antagonism of the estrogen receptor (ER) or by the inhibition of the estrogen synthesis. Our interest in identifying a bioactive compound rich in polyphenols, which induces both the antagonism of the estrogen receptor, and the inhibition of the estrogen synthesis, revealed us the pomegranate fruit and its derivatives: peel and seeds. Pomegranates' chemical composition include many biological active substances such as flavonols, flavanols, anthocyanins, proanthocyanidins, ellagitannins and gallotannins. Materials and Methods: We performed a review of the scientific literature by using the following keywords: "pomegranate", "breast cancer", "Punica granatum", "pomegranate polyphenols". Our search was performed in the PubMed and Google Scholar databases, and it included only original research written in English from the last 20 years. None of the articles were excluded due to affiliation. A total number of 28 original papers, which mentioned the beneficial activity of pomegranate against breast cancer, were selected. Both clinical and preclinical studies were considered for this review. Results: Recent discoveries pointed out that polyphenols from Punica granatum possess strong anti-cancer activity, exhibited by a variety of mechanisms, such as anti-estrogenic, anti-proliferative, anti-angiogenetic, anti-inflammatory, and anti-metastatic. Pomegranate extracts induced cell cycle arrest in the G0/G1 phase, and induced cytotoxicity in a dose- and time-dependent manner. Moreover, several polyphenols extracted from pomegranate inhibited the invasion potential, migration and viability of breast cancer cells. The effects of pomegranate juice on serum estrogens and other sexual hormones levels were also investigated on two human cohorts. Conclusions: Punica granatum represents a promising area in oncology. The large availability and low cost, associated with the lack of side effects, made from this natural product a great strategy for the management of breast cancer. There are several mechanistic studies in mouse models and in breast cancer cell lines, suggesting the possible pathways through which polyphenols from pomegranate extracts act, but larger and better-controlled studies are necessary in the future. Only two small clinical trials were conducted on humans until now, but their results are contradictory and should be considered preliminary.

Toxic Blood Hydrogen Cyanide Concentration as a Vital Sign of a Deceased Room Fire Victim-Case Report.

Carbon monoxide (CO) and hydrogen cyanide (HCN) are two common toxic products of combustion. HCN concentrations of fire victims are not routinely determined in most legal medicine services in Romania. We present the case of a room fire victim in which we evaluated the concentrations of HCN and carboxyhemoglobin (COHb), their contribution to the mechanism of death, and the possibility that HCN concentration can be interpreted as vital sign. COHb was determined by spectrophotometry. HCN was spectrophotometrically determined with ninhydrin in postmortem blood samples after its removal with 20% phosphoric acid and uptake into a solution of potassium carbonate. The presence of ethyl alcohol was determined by gas chromatography. The COHb concentration was 6.15%, while the blood HCN concentration was 1.043 µg × mL-1 and the total HCN was 1.904 µg × ml-1. A blood alcohol content of 4.36 g‰ and a urine alcohol content of 5.88 g‰ were also found. Although the fire produced a considerable amount of soot, and there were signs of inhalation of soot particles, the COHb level cannot be interpreted as a vital sign. Toxic concentrations of HCN and total HCN can be interpreted as a vital sign and indicates a contributive effect of HCN in the mechanism of death.

Risk management strategies and therapeutic modalities to tackle COVID-19/SARS-CoV-2.

The recent emergence of novel coronavirus disease (COVID-19) triggered by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in substantial mortality worldwide. Presently, there is no approved treatment for COVID-19. Consequently, the clinical, scientific, and regulatory authorities have joint efforts to reduce the severe impact of COVID-19. To date, there is minimal arsenal with no definite curative drugs, licensed-vaccines, or therapeutic conducts to combat the COVID-19 infections. Keeping in view the threats of this pandemic, various global organizations, physicians, researchers, and scientists, are trying to recognize the epidemiological characteristics and pathogenic mechanisms of COVID-19 to discover potential treatment regimens, vaccines, and therapeutic modes for future anticipation. Herein, we summarize a contemporary overview of curative invasions and vaccines for COVID-19 based on the earlier information and considerate of similar earlier RNA coronaviruses. The information reviewed here establishes a paramount intellectual basis to promote ongoing research to develop vaccines and curative agents. Thus, this review suggests the furthermost accessible frontiers in the vaccine development to tackle or combat the COVID-19/SARS-CoV-2.

Are Bioactive Molecules from Seaweeds a Novel and Challenging Option for the Prevention of HPV Infection and Cervical Cancer Therapy?-A Review.

Cervical cancer represents one of the leading causes of cancer-related death in women all over the world. The infection with human papilloma virus (HPV) is one of the major risk factors for the development of premalignant lesions, which will progress to cervical cancer. Seaweeds are marine organisms with increased contents of bioactive compounds, which are described as potential anti-HPV and anti-cervical cancer agents. Our study aims to bring together all the results of the previous studies, conducted in order to highlight the potency of bioactive molecules from seaweeds, as anti-HPV and anti-cervical agents. This paper is a review of the English literature published between January 2010 and August 2020. We performed a systematic study in the Google Academic and PubMed databases using the key words "HPV infection", "anticancer", "seaweeds", "cervical cancer" and "carcinogenesis process", aiming to evaluate the effects of different bioactive molecules from marine algae on cervical cancer cell lines and on HPV-infected cells. Only original studies were considered for our research. None of the papers was excluded due to language usage or affiliation. Recent discoveries pointed out that sulfated polysaccharides, such as dextran sulfate heparan or cellulose sulfate, blocked the ability of HPV to infect cells, and inhibited the carcinogenesis process. Carrageenans inhibited the virions of HPV from binding the cellular wall. Fucoidan induced the growth inhibition of HeLa cervical cells in vitro. Heterofucans exhibited antiproliferative effects on cancer cell lines. Terpenoids from brown algae are also promising agents with anti-cervical cancer activity. Considering all the results of the previous studies, we observed that great amounts of bioactive molecules from seaweeds could treat both unapparent HPV infection and clinical visible disease. Furthermore, these molecules were very efficient in the treatment of invasive cervical carcinomas. In these conditions, we consider seaweeds extracts as a novel and challenging therapeutic strategy, and we hope that our study paves the way for further clinical trials in the field.

Hydrogen cyanide and carboxyhemoglobin assessment in an open space fire-related fatality.

Hydrogen cyanide (HCN) can be a major contributory factor in death from fire-related inhalation injury. Although carbon monoxide (CO) is considered the lethal agent of smoke in fires, its liability as a cause of death is sometimes debatable. The purpose of this report is to present the case of an 80-year-old man with locomotor disabilities who died due to an open space fire of vegetation debris and household waste in his yard. We evaluated here the concentrations of HCN and carboxyhemoglobin (COHb) and their contribution to the mechanism of death. In addition, the risk factors and the contributing effect of the factors that compose the complex toxic environment that develops in fires were discussed. COHb was determined by spectrophotometry as recommended by Katsumata et al. in 1982. HCN was determined with ninhydrin in postmortem blood samples after removal with 20% phosphoric acid and capture in a potassium carbonate solution. A toxic concentration of 1.3 µg ml-1 HCN and a lethal COHb level of 73.7% were determined in the blood samples. Although death was mainly attributed to CO poisoning and extremely severe burns in this open space burning case, the additive effect of HCN in the mechanism of death was also highlighted. The results suggested the possibility that the man's clothing may have played an important role in the production of HCN in this open space fire, as well as other types of garbage that were burned.

Royal Jelly-A Traditional and Natural Remedy for Postmenopausal Symptoms and Aging-Related Pathologies.

Women's life stages are based on their reproductive cycle. This cycle begins with menstruation and ends with menopause. Aging is a natural phenomenon that affects all humans, and it is associated with a decrease in the overall function of the organism. In women, aging is related with and starts with menopause. Also, during menopause and postmenopausal period, the risk of various age-related diseases and complaints is higher. For this reason, researchers were pushed to find effective remedies that could promote healthy aging and extended lifespan. Apitherapy is a type of alternative medicine that uses natural products from honeybees, such as honey, propolis, royal jelly, etc. Royal jelly is a natural yellowish-white substance, secreted by both hypopharyngeal and mandibular glands of nurse bees, usually used to feed the queen bees and young worker larvae. Over the centuries, this natural product was considered a gold mine for traditional and natural medicine, due to its miraculous effects. Royal jelly has been used for a long time in commercial medical products. It has been demonstrated to possess a wide range of functional properties, such as: antibacterial, anti-inflammatory, vasodilatative, hypotensive, anticancer, estrogen-like, antihypercholesterolemic, and antioxidant activities. This product is usually used to supplement various diseases such as cardiovascular disease, Alzheimer's disease, sexual dysfunctions, diabetes or cancer. The main objective of this study is to highlight the effectiveness of royal jelly supplementation in relieving menopause symptoms and aging-related diseases. We also aimed to review the most recent research advances regarding the composition of royal jelly for a better understanding of the effects on human health promotion.

Correlations between endothelial cell markers CD31, CD34 and CD105 in colorectal carcinoma.

PURPOSE: Colorectal carcinoma is an important cause of mortality worldwide. The fact that tumor growth is dependent on angiogenesis has supported researches for new prognostic parameters and the development of novel therapeutic strategies. Accordingly, we sought to evaluate angiogenesis quantitatively by assessing microvessel density in colorectal cancer. MATERIALS AND METHODS: The blood vessels stained with CD31, CD34 and CD105 were counted, and we reported their number per square millimeter in order to obtain microvascular density (MVD). Then, we aimed at comparing the performance of three endothelial cell markers (CD31, CD34, and CD105) on formalin-fixed tissues from 58 patients diagnosed with colorectal cancer. RESULTS: Following the comparison of the average effective vessels marked with the three markers, Student's t-test showed that the mean number of blood vessels marked with CD34 is higher than the blood vessels marked with CD31 and CD105. A significant difference that has been registered between the three levels of the T stage was found in the patients in our study, in terms of value marker CD105, ANOVA p=0.049, which returns to a value <0.05. Quick time decreases the pT stage, the observed differences being close to statistical significance. However, the result of ANOVA test does not allow us to say that differences can be generalized and not just a particular result, valid only for the study group, p=0.061 >0.05. There is a significant difference between patients with stage T, in terms of value: hemoglobin (ANOVA p<0.001), hematocrit (ANOVA p<0.001), mean corpuscular volume (MCV) (ANOVA p<0.001), mean corpuscular hemoglobin (MCH) (ANOVA p=0.002 <0.01 - significant difference with 99% confidence). By calculating the Pearson's correlation coefficient for the relationship CD31-CD105, we obtained a value r=0.440, which corresponds to p=0.0013 <0.05, indicating a statistically noteworthy direct correlation between the two factors. CONCLUSIONS: CD31 marker increases simultaneously with the CD105, in the cases analyzed throughout the present study. The ability of tumors to maintain a high vascular blood density in their inner portions may represent a reliable parameter to evaluate tumor angiogenesis and a finding relevant for future development of therapeutic angiogenesis strategies.