Ellagitannins and simple phenolics from the halophytic plant Tamarix nilotica.

Three new [nilotinins M8‒M10 (1‒3)] and two known [tamarixinin A (4) and gemin D (5)] ellagitannins and seven simple phenolics [gallic acid (6), methyl gallate (7), 3,4-di-O-methylgallic acid (8), ellagic acid (9), 3-O-methylellagic acid (10), methyl ferulate 3-O-sulphate (11), and 7,4'-di-O-methylkaempferol (12)] were isolated from the halophytic plant Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae). Their structures were determined based on intensive spectroscopic studies and comparisons with reported data. Compounds 4, and 6-8 were evaluated for their cytotoxicity against lung adenocarcinoma cell line (A549) and anti-leishmanial activity against Leishmania major. Compounds 4, 6 and 7 showed promising cytotoxic properties against A549 (IC50 29 ± 2.3, 10.5 ± 0.7, and 20.7 ± 1.9 µg/mL), while compounds 4 and 7 showed higher growth-inhibitory effects against L. major promastigotes (IC50 40.5 ± 2.7 and 38.4 ± 2.5 µg/mL), as compared with the standards doxorubicin (IC50 0.42 µg/mL) and miltefosine (IC50 9.43 µg/mL), respectively.

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation.

BACKGROUND: Pancreatic cancer is one of the most serious and lethal human cancers with a snowballing incidence around the world. The natural product celastrol has also been widely documented as a potent anti-inflammatory, anti-angiogenic, and anti-oxidant. PURPOSE: To elucidate the antitumor effect of celastrol on pancreatic cancer cells and its modulatory role on whole genome expression. METHODS: The antitumor activity of celastrol on a panel of pancreatic cancer cells has been evaluated by Sulforhodamine B assay. Caspase 3/7 and histone-associated DNA fragments assays were done for apoptosis measurement. Additionally, prostaglandin (PGE2) inhibition was evaluated. Moreover, a microarray gene expression profiling was carried out to detect possible key players that modulate the antitumor effects of celastrol on cells of pancreatic cancer. RESULTS: Our findings indicated that celastrol suppresses the cellular growth of pancreatic cancer cells, induces apoptosis, and inhibits PGE2 production. Celastrol modulated many signaling genes and its cytotoxic effect was mainly mediated via over-expression of ATF3 and DDIT3, and down-expression of RRM2 and MCM4. CONCLUSION: The current study aims to be a starting point to generate a hypothesis on the most significant regulatory genes and for a full dissection of the celastrol possible effects on each single gene to prevent the pancreatic cancer growth.

Synergistic Effect of Mandarin Peels and Hesperidin with Sodium Nitrite against Some Food Pathogen Microbes.

Food preservatives such as NaNO2, which are widely used in human food products, undoubtedly affect, to some extent, human organs and health. For this reason, there is a need to reduce the hazards of these chemical preservatives, by replacing them with safe natural bio-preservatives, or adding them to synthetic ones, which provides synergistic and additive effects. The Citrus genus provides a rich source of such bio-preservatives, in addition to the availability of the genus and the low price of citrus fruit crops. In this study, we identify the most abundant flavonoids in citrus fruits (hesperidin) from the polar extract of mandarin peels (agro-waste) by using spectroscopic techniques, as well as limonene from the non-polar portion using GC techniques. Then, we explore the synergistic and additive effects of hesperidin from total mandarin extract with widely used NaNO2 to create a chemical preservative in food products. The results are promising and show a significant synergistic and additive activity. The combination of mandarin peel extract with NaNO2 had synergistic antibacterial activity against B. cereus, Staph. aureus, E. coli, and P. aeruginosa, while hesperidin showed a synergistic effect against B. cereus and P. aeruginosa and an additive effect against Staph. aureus and E. coli. These results refer to the ability of reducing the concentration of NaNO2 and replacing it with a safe natural bio-preservative such as hesperidin from total mandarin extract. Moreover, this led to gaining benefits from their biological and nutritive values.

Antiviral zinc oxide nanoparticles mediated by hesperidin and in silico comparison study between antiviral phenolics as anti-SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus (COVID-19), is the virus responsible for over 69,613,607 million infections and over 1,582,966 deaths worldwide. All treatment measures and protocols were considered to be supportive only and not curative. During this current coronavirus pandemic, searching for pharmaceutical or traditional complementary and integrative medicine to assist with prevention, treatment, and recovery has been advantageous. These phytopharmaceuticals and nutraceuticals can be more economic, available, safe and lower side effects. This is in silico comparison study of ten phenolic antiviral agents against SARS-CoV-2, as well as isolation of the most active metabolite from natural sources. Zinc oxide nanoparticles (ZnO NPs) were also then prepared using these metabolite as a reducing agent. All tested compounds showed predicted anti-SARS-CoV-2 activity. Hesperidin showed the highest docking score, this leads us to isolate it from the orange peels and we confirmed its structure by conventenional spectroscopic analysis. In addition, synthesis of hesperidin zinc oxide nanoparticles was characterized by UV, IR, XRD and TEM. In vitro antiviral activity of hesperidin and ZnO NPs was evaluated against hepatitis A virus as an example of RNA viruses. However, ZnO NPs and hesperidin showed antiviral activity against HAV but ZnO NPs showed higher activity than hesperidin. Thus, hesperidin and its mediated ZnO nanoparticles are willing antiviral agents and further studies against SARS-CoV-2 are required to be used as a potential treatment.

Rutin and Selenium Co-administration Reverse 3-Nitropropionic Acid-Induced Neurochemical and Molecular Impairments in a Mouse Model of Huntington's Disease.

Systemic administration of 3-nitropropionic acid (3-NPA) is commonly used to induce Huntington's disease (HD)-like symptoms in experimental animals. Here, the potential neuroprotective efficiency of rutin and selenium (RSe) co-administration on 3-NPA-induced HD-like symptoms model in mice was investigated. 3-NPA injection evoked severe alterations in redox status, as indicated via increased striatal malondialdehyde and nitric oxide levels, accompanied by a decrease in levels of antioxidant molecules including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Moreover, 3-NPA potentiated inflammatory status by enhancing the production of interleukin-1ß, tumor necrosis factor-α, and myeloperoxidase activity. Pro-apoptotic cascade was also recorded in the striatum as evidenced through upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. 3-NPA activated astrocytes as indicated by the upregulated glial fibrillary acidic protein and inhibited brain-derived neurotrophic factor. Furthermore, perturbations in cholinergic and monoaminergic systems were observed. RSe provided neuroprotective effects by preventing body weight loss, oxidative stress, neuroinflammation, and the apoptotic cascade. RSe inhibited the activation of astrocytes, increased brain-derived neurotrophic factor, and improved cholinergic and monoaminergic transmission following 3-NPA intoxication. Taken together, RSe co-administration may prevent or delay the progression of HD and its associated impairments through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory effects.

Women's knowledge of maternal danger signs during pregnancy: Findings from a cross-sectional survey in Papua New Guinea.

OBJECTIVE: To explore knowledge of pregnancy related danger signs among women attending antenatal clinics in Papua New Guinea. DESIGN: Cross-sectional survey undertaken as part of a wider integrated health and demographic survey. SETTING: Three sites in Papua New Guinea: Hiri District (Central Province), Karkar (Madang Province) and Asaro (Eastern Highlands Province). PARTICIPANTS: 482 women aged 15-44 years. FINDINGS: Almost all (95.2%; 459/482) women attended for antenatal care at least once; 68.2% attended four or more times. Among women who attended the antenatal clinic, 53.6% (246/459) reported receiving information about danger signs in pregnancy from a health worker. Of these 60.2% (148/246) could recall at least one danger sign. In addition, 16.4% (35/213) of women who did not receive information from the antenatal clinic reported pregnancy related danger signs. Among the 183 women who reported danger signs, 47.5% (87/183) reported fever; 39.3% (72/183) reported vaginal bleeding and 36.6% (67/183) reported swelling of the face, legs and arms. Women who reported receiving information at the antenatal clinic were significantly more likely know any danger signs, compared with women who did not receive information at the antenatal clinic (OR 7.68 (95%CI: 4.93, 11.96); p = <0.001). Knowledge of danger signs was significantly associated with secondary school education, compared with none or only primary education (OR 3.08 (95% CI: 2.06, 4.61); p = <0.001). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Every antenatal clinic visit should be used opportunistically to provide women with information about key danger signs during pregnancy and childbirth. Recognising maternal danger signs, together with the importance of seeking early transfer to the health facility and the importance of attending for a health facility birth are critical to improving outcomes for mothers and babies especially in low income settings such as Papua New Guinea.

Baseline study and risk analysis of landfill leachate - Current state-of-the-science of computer aided approaches.

For the successful completion of a risk analysis process, its foundation (i.e. a baseline study) has to be well established. For this purpose, a baseline study needs to be more integrated than ever, particularly when environmental legislation is increasingly becoming stringent and integrated. This research investigates and concludes that no clear evidence of computer models for baseline study has been found in a whole-system and integrated format, which risk assessors could readily and effectively use to underpin risk analyses holistically and yet specifically for landfill leachate. This is established on the basis of investigation of software packages that are particularly closely related to landfills. Holistic baseline study is also defined along with its implications and in the context of risk assessment of landfill leachate. The study also indicates a number of factors and features that need to be added to baseline study in order to render it more integrated thereby enhancing risk analyses for landfill leachate.

"Whenever they cry, I cry with them": Reciprocal relationships and the role of ethics in a verbal autopsy study in Papua New Guinea.

Verbal autopsy (VA) methods usually involve an interview with a recently bereaved individual to ascertain the most probable cause of death when a person dies outside of a hospital and/or did not receive a reliable death certificate. A number of concerns have arisen around the ethical and social implications of the use of these methods. In this paper we examine these concerns, looking specifically at the cultural factors surrounding death and mourning in Papua New Guinea, and the potential for VA interviews to cause emotional distress in both the bereaved respondent and the VA fieldworker. Thirty one semi-structured interviews with VA respondents, the VA team and community relations officers as well as observations in the field and team discussions were conducted between June 2013 and August 2014. While our findings reveal that VA participants were often moved to cry and feel sad, they also expressed a number of ways they benefited from the process, and indeed welcomed longer transactions with the VA interviewers. Significantly, this paper highlights the ways in which VA interviewers, who have hitherto been largely neglected in the literature, navigate transactions with the participants and make everyday decisions about their relationships with them in order to ensure that they and VA interviews are accepted by the community. The role of the VA fieldworker should be more carefully considered, as should the implications for training and institutional support that follow.

Serum apelin in early-onset neonatal sepsis: is it diagnostic?

OBJECTIVE: To evaluate the diagnostic value of serum apelin in early-onset neonatal sepsis in full term neonates. Apelin is a proinflammatory adipocyte-derived factor that participates in vascular wall inflammation. STUDY DESIGN: Case-control study was conducted on 60 full term neonates, 30 cases with early-onset neonatal sepsis and 30 healthy matched controls. Complete blood counts, C-reactive protein, blood cultures, plasma lactate, and serum apelin concentrations (measured by enzyme-linked immunosorbent assay) were determined initially at the time of sepsis diagnosis and 4 days after starting treatment for cases. Only basal serum apelin concentrations were measured for control group. RESULTS: Apelin was detected in all neonates and concentrations were positively correlated to sepsis scores, plasma lactate and CRP. Neonates with sepsis had significantly elevated concentrations (8 folds increase) of serum apelin concnetration as compared to controls [median (IQR): 65.16(46.90) and 7.969(11.36) pg/ml, respectively]. Moreover initial serum apelin concentration measured in cases with culture proven neonatal sepsis was significantly higher than those with negative-culture clinical sepsis (mean ± SD: 73.53 ± 31.77 and 45.22 ± 5.9 respectively, p = 0.0001). The best cutoff value of serum apelin to diagnose early-onset neonatal sepsis was 30.225 pg/ml with a sensitivity of 100% and a specificity of 97%. CONCLUSION: Serum apelin may have a diagnostic value in early-onset neonatal sepsis.

Literature review of baseline study for risk analysis - the landfill leachate case.

There is growing awareness and public concern about environmental impacts of waste management and disposal. Environmental policy instruments have been strengthened and associated governmental programmes have increased in recent years, resulting in high level strategies for waste management. Risk assessment is now an essential tool in the prioritisation of environmental and human health protection. However, regulators need to compare the full range of risks on a sound and consistent basis. Comparing risks from such diverse sources poses a significant challenge, and traditional hazard and risk assessments are no longer sufficient. Consideration now needs to be given to a much wider range of factors if risk assessment is to be used as an aid to more integrated decision-making process. For this purpose, baseline study - the foundation of risk assessment - can play a crucial role. To date limited research has been conducted on the need, parameters, requirements, and constituents of baseline study particularly in the context of how, why, and what information is to be collated in order to render risk assessments more appropriately integrated and complete. To establish the 'state-of-the-art' of baseline study, this paper comprehensively reviews the literature regarding environmental risk assessment in general terms, and then proceeds to review work that is specifically related to landfills and landfill leachate, thereby identifying knowledge gaps and shortfall areas. This review concludes that a holistic baseline study procedure for waste disposal sites, which risk assessors could use for carrying out risk analyses specifically for landfill leachate, does not as yet exist.

Lead level in pregnant women suffering from pre-eclampsia in Dakahlia, Egypt.

BACKGROUND: Lead toxicity is a prevalent health problem in both developed and developing countries. One of the proposed mechanisms for lead-induced organ damage is oxidative stress. Oxidative stress is well-associated with the pregnancy disorder, pre-eclampsia. Exposure to lead may be one of the sources of the oxidative stress that leads to development of pre-eclampsia in pregnant women. OBJECTIVE: To test if blood lead level of pregnant women suffering from pre-eclampsia is higher than the normal limit. METHODS: Using atomic absorption spectrophotometry, blood lead level was measured in 115 pregnant women suffering from pre-eclampsia and compared to its level in a comparison group of 25 healthy pregnant women in Dakahlia governorate, Egypt. RESULTS: The mean±SD blood lead level was 37.68±9.17 µg/dL in women with pre-eclampsia; the value in the comparison group was 14.5±3.18 µg/dL (p<0.001). CONCLUSION: Pre-eclampsia is significantly associated with a high blood lead level.

Autologous melanocyte-keratinocyte suspension in the treatment of vitiligo.

BACKGROUND: In stable vitiligo, several techniques of autologous transplantation of melanocytes are used. Autologous melanocyte transplantation of non-cultured melanocytes is one of those techniques with variable reported outcomes. OBJECTIVE: The objective of this study was to evaluate the response to autologous melanocyte-keratinocytes suspension transplantation in cases of stable vitiligo. METHODS: A total of 25 cases of vitiligo were treated by autologous melanocyte-keratinocytes suspension transplantation. After 6-17 months, patients' response was evaluated according to the extent of pigmentation (excellent 90-100%, good 50-89%, fair 20-49% and poor response <20%). RESULTS: Of the 25 patients treated, 22 continued the follow-up period. Five (23%) patients showed excellent response, 7 (32%) good, 6 (27%) fair and 4(18%) showed poor response. CONCLUSION: Unlike transplantation of cultured melanocytes, which requires experience in culture technique, autologous melanocyte-keratinocytes suspension transplantation is an easy economic technique, which may be used in resistant areas of stable vitiligo.

Sociodemographic factors associated with maternal health care utilization in Wosera, East Sepik Province, Papua New Guinea.

This retrospective study sought to describe the utilization of maternal health services in a rural community in Wosera, East Sepik Province, Papua New Guinea. Interviews were undertaken with a convenience sample of 391 women of reproductive age. We examined the relationship between socioeconomic and demographic characteristics and the use of antenatal clinic services and delivery at a health centre. Despite uptake of antenatal care services by 79% of women, two-thirds of women gave birth at home. Women's education was an independent predictor for maternal health care utilization, for both antenatal care and delivery at a health facility. At least one visit to an antenatal clinic was the strongest predictor of delivering at a health care facility. Women expressed barriers to assisted childbirth such as distance to health facilities, especially when labour came fast, and feelings of shame in presenting to a facility to give birth. This study provides important information relating to the uptake of maternal health care services. Despite the uptake of available antenatal care services, intrapartum services are not well accessed.

Consent--its medico legal aspects.

One of the duties of a doctor towards his patients is to obtain consent before any medical examination. Any such examination without prior consent amounts to an assault on the patient. Consent is defined under Indian Contract Act (because Doctor Patient relationship isa contract) as "two or more persons are said to consent when they agree to the same thing in the same sense." Consent may be implied, expressed or informed depending upon the circumstances. But the consent of the patient is not required in situations like medical emergency, for vaccination etc. If the patient is not medically or legally competent to give consent, the consent of the parents or guardians or any person present at the time with the patient can be taken. Any research on a potential subject, removal of organs for transplantation, publication of information obtained during medical examination also require consent of the concerned person.

Life cycle analysis and sewer solids.

The search for sustainable ways of living has necessitated a new look at the way in which water services are provided. The new paradigm includes whole-system perspectives for each of the primary criteria groups: social, environmental and economic. Whilst Life Cycle Analysis (LCA) techniques have been used successfully for products, they are much less used to assess processes. Nonetheless there is much to learn from the use of LCA for a much wider range of applications. An application is described whereby LCA has been used to determine energy, mass flows and environmental impacts for a number of sewer-related options for handling sewer solids, using the SimaPro software. This work has been part of a wider study to provide enhanced decision support systems for water utilities.

Rational procedure for 3D-QSAR analysis using TRNOE experiments and computational methods: application to thermolysin inhibitors.

The success or failure of 3D QSAR, particularly CoMFA, is most strongly dependent, especially for flexible compounds, on the conformation of the molecule used in the analysis, and on the orientation of the molecule relative to the other molecules in 3D space (i.e., alignment). The present study suggests a rational procedure for the estimation of binding conformation that uses the transferred nuclear Overhauser effect (TRNOE) experiment in combination with conformational analysis using CAMDAS (Conformational Analyzer with Molecular Dynamics And Sampling) program that is developed in our laboratory. In the next step the TRNOE-obtained conformation can be used as a reference template in order to obtain alignment of other ligands, that have a common binding site. In this step we used the SUPERPOSE program created in our laboratory, in order to estimate the binding conformation of other compounds, and to simultaneously obtain the alignment of compounds for CoMFA. The resulting CoMFA models could be expected to closely reproduce the interaction mode with protein represented by the reported X-ray results. In order to confirm the validity of our procedure described above, we show its application in obtaining CoMFA models of thermolysin inhibitors. We obtained twenty CoMFA models, and that with the highest q2 value (q2 = 0.701) was found to provide an interaction mode very similar to that represented by the X-ray results.

Refinement of the NMR structures of alpha-conotoxin MI using molecular dynamics simulation with explicit solvent water and a full molecular force field.

Three NMR structures of alpha-conotoxin MI, a potent antagonist of the nicotinic acetylcholine receptor, have been refined using molecular dynamics (MD) simulation with explicit water. Although the convergence of the NMR structures of alpha-conotoxin MI was not sufficient to provide detailed structural features, the average structures obtained from MD simulations converged to one conformation, providing structural characteristics. The resulting structure was also found to be consistent with the results of amide proton-exchange experiments. These results demonstrate that MD simulation with explicit solvent water is very useful in refining NMR structures.

Three-dimensional structure-activity relationship analysis between motilin and motilide using conformational analysis and a novel molecular superposing method.

Motilide, an erythromycin derivative, has been shown to equal activity to that of motilin as an agonist at the motilin receptor. However, there is little information on the three-dimensional (3D) structure-activity relationship between these two molecules, largely because they have quite different structures. In this study, we applied a rational computational procedure consisting of conformational analysis and a novel superposing method to investigate the 3D structure-activity relationship between motilide and motilin. We propose common 3D structural features between these molecules, which may be important for their similar activity.