Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy - A comprehensive review.

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Spike Protein Variants.

The slow experimental acquisition of high-quality atomic structures of the rapidly changing proteins of the COVID-19 virus challenges vaccine and therapeutic drug development efforts. Fortunately, deep learning tools such as AlphaFold2 can quickly generate reliable models of atomic structure at experimental resolution. Current modeling studies have focused solely on definitions of mutant constellations of Variants of Concern (VOCs), leaving out the impact of haplotypes on protein structure. Here, we conduct a thorough comparative structural analysis of S-proteins belonging to major VOCs and corresponding latitude-delimited haplotypes that affect viral seasonal behavior. Our approach identified molecular regions of importance as well as patterns of structural recruitment. The S1 subunit hosted the majority of structural changes, especially those involving the N-terminal domain (NTD) and the receptor-binding domain (RBD). In particular, structural changes in the NTD were much greater than just translations in three-dimensional space, altering the sub-structures to greater extents. We also revealed a notable pattern of structural recruitment with the early VOCs Alpha and Delta behaving antagonistically by suppressing regions of structural change introduced by their corresponding haplotypes, and the current VOC Omicron behaving synergistically by amplifying or collecting structural change. Remarkably, haplotypes altering the galectin-like structure of the NTD were major contributors to seasonal behavior, supporting its putative environmental-sensing role. Our results provide an extensive view of the evolutionary landscape of the S-protein across the COVID-19 pandemic. This view will help predict important regions of structural change in future variants and haplotypes for more efficient vaccine and drug development.

Seasonal effects decouple SARS-CoV-2 haplotypes worldwide.

Background: Variants of concern (VOCs) have been replacing each other during the still rampant COVID-19 pandemic. As a result, SARS-CoV-2 populations have evolved increasingly intricate constellations of mutations that often enhance transmissibility, disease severity, and other epidemiological characteristics. The origin and evolution of these constellations remain puzzling. Methods: Here we study the evolution of VOCs at the proteome level by analyzing about 12 million genomic sequences retrieved from GISAID on July 23, 2022. A total 183,276 mutations were identified and filtered with a relevancy heuristic. The prevalence of haplotypes and free-standing mutations was then tracked monthly in various latitude corridors of the world. Results: A chronology of 22 haplotypes defined three phases driven by protein flexibility-rigidity, environmental sensing, and immune escape. A network of haplotypes illustrated the recruitment and coalescence of mutations into major VOC constellations and seasonal effects of decoupling and loss. Protein interaction networks mediated by haplotypes predicted communications impacting the structure and function of proteins, showing the increasingly central role of molecular interactions involving the spike (S), nucleocapsid (N), and membrane (M) proteins. Haplotype markers either affected fusogenic regions while spreading along the sequence of the S-protein or clustered around binding domains. Modeling of protein structure with AlphaFold2 showed that VOC Omicron and one of its haplotypes were major contributors to the distortion of the M-protein endodomain, which behaves as a receptor of other structural proteins during virion assembly. Remarkably, VOC constellations acted cooperatively to balance the more extreme effects of individual haplotypes. Conclusions: Our study uncovers seasonal patterns of emergence and diversification occurring amid a highly dynamic evolutionary landscape of bursts and waves. The mapping of genetically-linked mutations to structures that sense environmental change with powerful ab initio modeling tools demonstrates the potential of deep-learning for COVID-19 predictive intelligence and therapeutic intervention.

Enhancements in yield, agronomic, and zinc recovery efficiencies of rice-wheat system through bioactive zinc coated urea application in Aridisols.

BACKGROUND: Zinc (Zn) deficiency and source-dependent Zn fertilization to achieve optimum Zn levels in rice and wheat grains remain global concern for human nutrition, especially in developing countries. To-date, little is known about the effectiveness of bioactive Zn-coated urea (BAZU) to enhance the concentration, uptake, and recovery of Zn in relation to agronomic efficiency in paddy and wheat grains. RESULTS: Field experiments were carried out during 2020-21 on the rice-wheat system at Lahore, Faisalabad, Sahiwal, and Multan, Punjab, Pakistan using four treatments viz.T1 (Urea 46% N @ 185 kg ha-1 + zero Zn), T2 (Urea 46% N @ 185 kg ha-1 + ZnSO4 33% Zn @ 15 kg ha-1), T3 (BAZU 42% N @ 103 kg ha-1 + Urea 46% N @ 62 kg ha-1 + 1% bioactive Zn @ 1.03 kg ha-1) and T4 (BAZU 42% N @ 125 kg ha-1 + Urea 46% N @ 62 kg ha-1 + 1% bioactive Zn @ 1.25 kg ha-1) in quadruplicate under Randomized Complete Block Design. Paddy yield was increased by 13, 11, 12, and 11% whereas wheat grain yield was enhanced by 12, 11, 11, and 10% under T4 at Multan, Faisalabad, Sahiwal, and Lahore, respectively, compared to T1. Similarly, paddy Zn concentration was increased by 58, 67, 65 and 77% (32.4, 30.7, 31.1, and 34.1 mg kg-1) in rice whereas grain Zn concentration was increased by 90, 87, 96 and 97% (46.2, 43.9, 46.7 and 44.9 mg kg-1) in wheat by the application of BAZU (T4) at Multan, Faisalabad, Sahiwal, and Lahore, respectively, in comparison to T1. Zinc recovery was about 9-fold and 11-fold higher in paddy and wheat grains, respectively, under BAZU (T4) treatment relative to T2 while, the agronomic efficiency was enhanced up to 130% and 141% in rice and wheat respectively as compared to T2. CONCLUSION: Thus, T4 application at the rate of 125 kg ha-1 could prove effective in enhancing the rice paddy and wheat grain yield along with their Zn biofortification (∼34 mg kg-1 and ∼47 mg kg-1, respectively) through increased agronomic and Zn recovery efficiencies, the underlying physiological and molecular mechanisms of which can be further explored in future.

EVALUATING THE IMPACT OF EARLY NUTRITIONAL ASSESSMENT AND INTERVENTION IN HOSPITALIZED LIVER CIRRHOSIS PATIENTS.

BACKGROUND: Malnutrition is common in liver cirrhosis patients that is correlated with early complications, morbidity and mortality. OBJECTIVE: The purpose of the study was to assess nutritional status, impact of nutritional screening and intervention in liver cirrhosis patients by evaluating their actual energy and protein intake during hospital stay. METHODS: A cross sectional study was conducted wherein all patients' nutritional status was defined by Subjective Global Assessment tool. Adequate energy and protein supply were planned and executed by using individualized nutritional plan for patients with dietitian's collaboration. Anthropometric measurements included height, weight, body mass index, mid upper arm circumference, hand grip strength and triceps skin-fold thickness. Biochemical tests included haemoglobin, mean corpuscular haemoglobin, volume and concentration, albumin and liver function tests. To record the daily food intake, a 24-hour dietary recall was used. RESULTS: Overall 83 patients (mean age 55) were included, among them 46% of patients were moderately malnourished, 12% were normal, while 42% of cirrhotic patients were severely depleted according to Subjective Global Assessment. The mean intake of calories and protein was improved during stay in hospital after nutritional intervention and critical monitoring (P<0.05). Anthropometric measurements at baseline and discharge showed significant differences (P <0.05) in weight, body mass index, triceps skin fold thickness and mid upper arm circumference values, but not in hand grip strength that was associated with malnourishment among patients. CONCLUSION: Providing individualized nutritional intervention and its monitoring by qualified dietitians during hospital stay helps to improve intake in patients that prevent further risk of malnutrition and related complications.

Impacto da avaliação nutricional precoce e intervenção em pacientes com cirrose hepática / Evaluating the impact of early nutritional assessment and intervention in hospitalized liver cirrhosis patients

ABSTRACT Background Malnutrition is common in liver cirrhosis patients that is correlated with early complications, morbidity and mortality. Objective The purpose of the study was to assess nutritional status, impact of nutritional screening and intervention in liver cirrhosis patients by evaluating their actual energy and protein intake during hospital stay. Methods A cross sectional study was conducted wherein all patients' nutritional status was defined by Subjective Global Assessment tool. Adequate energy and protein supply were planned and executed by using individualized nutritional plan for patients with dietitian's collaboration. Anthropometric measurements included height, weight, body mass index, mid upper arm circumference, hand grip strength and triceps skin-fold thickness. Biochemical tests included haemoglobin, mean corpuscular haemoglobin, volume and concentration, albumin and liver function tests. To record the daily food intake, a 24-hour dietary recall was used. Results Overall 83 patients (mean age 55) were included, among them 46% of patients were moderately malnourished, 12% were normal, while 42% of cirrhotic patients were severely depleted according to Subjective Global Assessment. The mean intake of calories and protein was improved during stay in hospital after nutritional intervention and critical monitoring (P<0.05). Anthropometric measurements at baseline and discharge showed significant differences (P <0.05) in weight, body mass index, triceps skin fold thickness and mid upper arm circumference values, but not in hand grip strength that was associated with malnourishment among patients. Conclusion Providing individualized nutritional intervention and its monitoring by qualified dietitians during hospital stay helps to improve intake in patients that prevent further risk of malnutrition and related complications.

RESUMO Contexto A desnutrição é comum em pacientes com cirrose hepática e está correlacionada com complicações precoces, morbidade e mortalidade. Objetivo O objetivo do estudo foi avaliar o estado nutricional, o impacto da triagem nutricional e a intervenção em pacientes com cirrose hepática, avaliando sua ingestão real de energia e proteína durante a internação hospitalar. Métodos Foi realizado um estudo transversal em que o estado nutricional de todos os pacientes foi definido pela ferramenta de Avaliação Global Subjetiva. O fornecimento adequado de energia e proteína foi planejado e executado por meio de plano nutricional individualizado para pacientes com colaboração de nutricionista. As medidas antropométricas incluíram: altura, peso, índice de massa corporal, circunferência do braço médio, força de aderência da mão e espessura da dobra da pele tríceps. Os testes bioquímicos incluíram: hemoglobina, volume e concentração da hemoglobina corpuscular média, albumina e testes de função hepática. Para registrar a ingestão diária de alimentos, foi utilizado um recall dietético de 24 horas. Resultados Ao todo foram incluídos 83 pacientes (média de 55 anos), entre eles 46% dos pacientes estavam moderadamente desnutridos, 12% estavam normais, enquanto 42% dos pacientes cirróticos estavam severamente depletados de acordo com a Avaliação Global Subjetiva. A ingestão média de calorias e proteínas foi melhorada durante a internação hospitalar após intervenção nutricional e monitoramento crítico (P<0,05). As medidas antropométricas na linha de base e descarga apresentaram diferenças significativas (P< 0,05) em peso, índice de massa corporal, espessura da dobra da pele do tríceps e valores médios de circunferência do braço, mas não na força de aderência da mão que estava associada à desnutrição entre os pacientes. Conclusão Proporcionar intervenção nutricional individualizada e seu acompanhamento por nutricionistas qualificados durante a internação hospitalar ajuda a melhorar a ingestão em pacientes que previnem maior risco de desnutrição e complicações relacionadas.

Bioactive Nutrient Fortified Fertilizer: A Novel Hybrid Approach for the Enrichment of Wheat Grains With Zinc.

Zinc (Zn) is a critical micronutrient that synergizes nutrient use efficiency, and improves plant growth and human health. Low Zn bioavailability in soils affects produce quality and agricultural productivity worldwide ultimately inducing deficiency in humans and animals. Zn deficiency is a leading cause of malnutrition in underdeveloped countries where a widespread population depends upon staple cereals for daily intake of calories. Modern cereal cultivars are inherently low in Zn, eventually, plants need to be enriched with soil application of ZnSO4, but due to higher fixation losses, it becomes an inefficient source. Rhizosphere microbiome contains Zn-solubilizing bacteria (ZSB) that improve Zn bioavailability, thus increase the root function, Zn uptake, and plant growth. Niha Corp developed a hybrid process of bioactive nutrient fortified fertilizer (BNFF), which has been used to formulate Zabardast Urea (ZU) by coating bioactive Zn (BAZ) and ZSB on urea. Data obtained for 15 wheat varieties from 119 farmer field demonstration plots and eight replicated trials on 42 locations across multi-environment conditions conclude that ZU significantly improved the plant biomass and yield by 12% over non-Zn control and produced grains with 57 µg/g Zn contents, which can meet a major part of the recommended dietary allowance (RDA) of humans. The study recommends that this microbe-mediated hybrid invention (ZU) is a feasible approach to boost Zn bioavailability and Zn use efficiency, with enhanced yield and quality that may contribute to improve human health. To the best of our knowledge, this is the first wide-scale field testing of Zn enrichment in the grains of bread wheat using an innovative BNFF Urea Z technology.

Effects of galacto-oligosaccharide prebiotics in blood profile of severely acute malnourished children.

This study assessed the effects of galacto-oligosaccharides (Oligomate) on hematocrit, serum enzymes, total bilirubin levels, and serum electrolytes in controls and severely malnourished infants, with emphasis on gastrointestinal symptoms. Oligomate doses and phases did not affect stools frequency per day, indicating that prebiotic effect on stool may be due to the prebiotic type. The number of vomits per day during phases 2 and 3 were significantly reduced (p<0.05) in response to prebiotics, despite the prebiotic dose effect was not significant (p>0.05). Moreover, prebiotics administration during phases 2 and 3 markedly improved hemoglobin levels (p<0.05), but not the dose. Similarly, hematocrit levels and white blood cells were significantly improved during the last 2 phases, but dose have no effects on blood hematocrit levels. Erythrocyte sedimentation rate significantly decreased (p<0.05) in phases 2 and 3 compared to phase 1. No dose-related effect was stated on erythrocytes sedimentation rate. Regarding the serum enzymes, SGPT significantly decreased (p<0.05) in phases 2 and 3 compared to phase 1, whereas SGOT significantly decreased only in phase 3. Total bilirubin levels increased significantly (p<0.05) in phase 3 when compared to phases 1 or 2. Prebiotics significantly decreased (p<0.05) sodium levels in the treated group, while potassium levels did not change in all groups, excepting during phase 2, where it increased significantly. Thus, our results confirm the hypothesis that prebiotic supplementation improves blood parameters and health status, consequently decreasing the infection risk and number of vomit per day in infants.

Bio-therapeutics effects of probiotic strain on the gastrointestinal health of severely acute malnourished children.

The core objective was to evaluate the effect of probiotic fortification at three phases of formula milk administration in malnourished children. A dose related effect was determined in 30 severely acute malnourished children (6-59 months) in a double-blind, randomized design. According to the results, serum albumin levels, treatment T2 (6 billion cfu) has significantly increased albumin levels (3.7g/dL) and the effect of phase-III (Plumpy'nut) was found to be better. Results regarding sodium levels showing probiotic-dose have significant effect (P≤0.05) in phases as well. Moreover, the effect of T1 i.e. 3 billion cfu of probiotics has significantly reduced sodium levels (141.8mmol/L) vs. others and the effect of phase-II was better on reducing sodium levels. which is further confirmed in terms of reduced erythrocyte sedimentation rate levels at phase-III (29.566 vs. phase-II, 41.3 and phase-I, 46.533 mm/h). Conclusively, the effect of 6 billion cfu at phase-III was more effective on blood parameters.

Association of life style and dietary habits with blood choline and cardiovascular outcome.

Whole-blood choline, plasma choline and serum choline are emerging biomarkers in cardiovascular diseases (CVD). To examine the association of Whole-blood choline is an early predictor for cardiac events. In case control study, we enrolled 240 individuals including 120 normal (39 females and 82 males) and 120 cases (49 females and 71 males) where age limit was >40 years) Information through interviews, family disease history, 24 recall diet assessment and blood sampling. Odds ratios express the associated risks with CVD and without CVD patients. In healthy populations, good dietary habits and active lifestyle were observed. The number of participants with CVD were smokers than normal. In men, and women the risk was observed highly significant. (p=0.0049) Different blood parameters like Triglycerides, Uric Acid, Urea, Creatinine, CRP and ESR were non-significant observed. In females the low carbohydrates and high protein and frequent salad vegetable consumption observed. On the other hand, men consume more carbohydrates. Body mass index was significantly with p= 0.036 (OD 1.12 95% 1.00-1.26). The total fats (p=0.017) (OD 1.3301 95% 1.05-1.69) total carbohydrate (p=0.076) (OD 1.1536 95% 0.98-1.35) and total proteins (p=0.287) (OD 1.1456 95% 0.89-1.47) effecting respectively.  The Blood choline level was significant observed between cases (p=0.026) OD (0.944 95%0.89- 0.99).

Preventive therapy of antioxidant vitamins against the blood choline levels in cardiovascular patients.

Therapeutic role of antioxidant against lipid profile and lipoprotein (choline) was observed by the different researchers, but  clinical evidences required about the use of antioxidant vitamins against the lipoproteins. Patients with clinical evidence of cardiovascular disease (CVD) confirmed by standard diagnostic techniques were followed. Newly or recently, diagnosed case subjects were recruited wherever possible. At least 120 cases, subjects both male and female with CVD were selected from a local hospital. Four groups developed on the base of antioxidant therapy and blood samples were collected at zero day, 20 days, 40 days and 60 days. vitamins C and E are the major dietary cellular and lipid antioxidants, respectively; we found no evidence to support the use of vitamin or antioxidant supplements in the reduction of mortality. However, they are helpful in the management of prevention of cardiovascular disease.

Prevalence of Toxoplasma gondii, Neospora caninum, and Sarcocystis Species DNA in the Heart and Breast Muscles of Rock Pigeons (Columbia livia).

Little is known about the prevalence of protozoan parasites in the muscles of rock pigeons (Columbia livia). The muscles from 54 (heart from 45 and breast from 54) rock pigeons were examined for DNA of Toxoplasma gondii, Neospora caninum, and Sarcocystis species using PCR. Twenty-four were female and 30 were males. The birds were part of flocks of pigeons housed at the tombs of saints in Lahore, Pakistan. Birds that died or were euthanized due to poor health were submitted for necropsy at the Department of Parasitology, University of Veterinary and Animal Sciences, Lahore, Pakistan, where DNA isolations and PCR were conducted. Nineteen (35.1%) of the birds were positive for T. gondii DNA. Seven males and 12 females were positive. Breast tissue was always infected in T. gondii positive birds, while the heart was infected in 13 (28.8%) of breast positive birds. Five (9.2%) of the pigeons, 2 males and 3 females, were positive for N. caninum. The distribution of N. caninum DNA was more variable in the muscles of pigeons than T. gondii and was found only in the heart of 1 (female), heart and breast muscle of 2 (male), and only the breast muscle of 2 birds (female). One of the 54 rock pigeons (female) was positive for both T. gondii (heart and breast) and N. caninum (heart only). Two of the positive Neospora caninum amplicons were sequenced and had 97% nucleotide identity with N. caninum isolates. Sarcocystis DNA was not found in any bird. The prevalence of T. gondii in rock pigeons and their predation by cats suggest that they may play an unrecognized role in maintaining environmental contamination with T. gondii oocysts by cats. Our study indicates that rock pigeons are intermediate hosts of N. caninum and this information will aid in understanding the epidemiology of N. caninum.