A Review - Colorectal Cancer, Prevalence, along with Screening, Diagnosis, and Novel Therapies

Colorectal cancer is considering a communal health problem and in the whole world, its number is third in all cancers that were diagnosed. It causes a significant burden in terms of sickness and death with the estimation of seven lakhs annual deaths. In many countries of the world western way of life is rapidly adopted that is a well-debated factor for colorectal cancer and in term of primary preventive measures, it could be besieged. Comparatively slow advancement of this cancer allows severe reduction of occurrence and death rate with the help of secondary prevention. These facts motivate primary care physicians to play a key role in health plans that improve prevention and rapid diagnosis. In ancient years, the targeted therapies with combinational treatment have proven to be very effective for specific colorectal cancer patients. These therapies are epidermal growth factor, receptor inhibitor, and growth factor. As the advancements in clinic and science have visible that give new treatment options for metastatic colorectal cancer, the five-year existence rate is still fourteen percent low. But in other subtypes of colorectal cancer, the results may not be successful and not highly explored. We can reduce side effects and make the treatment effect by using alternative therapies instead of traditional therapies such as anticancer drugs, probiotics, etc. Herein, some major topics related to CRC in recent literature have been reviewed, to acknowledge its malignancy, risk, and defensive factors, along with the screening methodologies. Moreover, we also debate over preventive as well as screening strategies to fight against CRC

Association of STAT4 rs7574865 with sysceptibility to juvenile onset systemic lupus erythematous in Pakistani population

Association of STAT4 (signal transducer and activator of transcription4) haplotype tagged by single nucleotide polymorphism (SNP) rs7574865 with systemic lupus erythematosus (SLE) was reported in different populations. This study was aimed to investigate a genetic association between STAT4 single nucleotide polymorphism (rs7574865) with susceptibility and clinical features of systemic lupus erythematosus in Pakistani population. A total of 75 clinically diagnosed individuals affected with SLE were enrolled from Children’s Hospital and Institute of Child Health Lahore. Sixty-eight healthy individuals of same ethnicity were also enrolled for this study. Clinical assessment of patients was done with the help of clinical features suggestive for SLE and some diagnostic tests specific for the disease were performed. SNP rs7574865 was genotyped by allele specific tetra ARMS PCR assay to check and compare the genotypic allele frequencies between SLE patients and healthy controls. Different statistical analysis ChiSquare, Fisher’s exact tests and binary Logistic Regression is performed to determine association of risk alleles with SLE in Pakistani population. p value less than >0.05 consider significant. This study showed the frequency of GG (28%), TT (12%), and GT alleles (60%) in SLE patients while controls showed allele frequencies of GG (5%), TT (29%) and GT (64%), respectively. The results showed that GG genotype and G allele in STAT4 rs7574865 was the risk allele for SLE while T allele proved to be the protective one for disease susceptibility when compared with healthy controls genotypic frequencies. This study suggests the strong association of SNP rs7574865 in STAT4 with the risk of SLE in Pakistani population. However, G allele showed no association with organ damage and immune disorder of SLE

Pharmacological screening of Viola Odorata L. for memory-enhancing effect via modulation of oxidative stress and inflammatory biomarkers

Purpose: Alzheimer disease (AD) is a progressive neurodegenerative disorder that is caused by neuroinflammation and oxidative stress. The present study aimed to characterize and then investigate the memory-enhancing potential of Viola odorata methanolic extract in lipopolysaccharide (LPS)–treated mice. Methods: V. odorata characterization was done by using the GCMS technique. Neuroinflammation was induced by the intracerebroventricular administration of LPS at a dose of 12 μg. Animals were divided randomly into six groups (n 10). Group I was normal control, which was given vehicle. Group II was disease control, which received LPS (12 μg) via the intracerebroventricular route. Group III was standard, which was administered with donepezil (3 μg) orally for 21 days. Groups IV–VI were the treatment groups, which were administered with the extract at 100, 200, and 400 mg/kg dose levels orally respectively for 21 days. Groups III–VI received LPS (12 μg) on the first day along with their treatments. During the treatment, the animals were assessed for memory retention by employing different behavioral paradigms namely elevated plus maze, passive avoidance, foot shock and open field. Various mediators [endogenous antioxidants, neurotransmitters, and acetylcholinesterase (AChE)] involved in the pathogenesis of AD were quantified by using the UV spectrophotometric method. Results: Extract-treated groups showed a remarkable improvement in cognitive impairment in all behavioral paradigms. Oxidative stress biomarkers, that is, superoxide dismutase, catalase, and glutathione were raised dose-dependently in the treatment groups with a dose-dependent decrease in the malonaldehyde and AChE levels in the brains of the treated animals. The treatment groups showed decreased levels of inflammatory biomarkers, that is, tumor necrosis factor–alpha, nuclear factor kappa light-chain enhancer of activated β-cells, and cyclo-oxygenase, which supports the therapeutic effectiveness of the treatment. Conclusion: Based on behavioral, oxidative stress biomarker, and neuroinflammatory data, it is concluded that V. odorata possesses memory-enhancing activity and may prove a beneficial role in the management of AD.peer-reviewe

Fungal systematics and evolution : FUSE 6

Fungal Systematics and Evolution (FUSE) is one of the journal series to address the “fusion” between morphological data and molecular phylogenetic data and to describe new fungal taxa and interesting observations. This paper is the 6th contribution in the FUSE series—presenting one new genus, twelve new species, twelve new country records, and three new combinations. The new genus is: Pseudozeugandromyces (Laboulbeniomycetes, Laboulbeniales). The new species are: Albatrellopsis flettioides from Pakistan, Aureoboletus garciae from Mexico, Entomophila canadense from Canada, E. frigidum from Sweden, E. porphyroleucum from Vietnam, Erythrophylloporus flammans from Vietnam, Marasmiellus boreoorientalis from Kamchatka Peninsula in the Russian Far East, Marasmiellus longistipes from Pakistan, Pseudozeugandromyces tachypori on Tachyporus pusillus (Coleoptera, Staphylinidae) from Belgium, Robillarda sohagensis from Egypt, Trechispora hondurensis from Honduras, and Tricholoma kenanii from Turkey. The new records are: Arthrorhynchus eucampsipodae on Eucampsipoda africanum (Diptera, Nycteribiidae) from Rwanda and South Africa, and on Nycteribia vexata (Diptera, Nycteribiidae) from Bulgaria; A. nycteribiae on Eucampsipoda africanum from South Africa, on Penicillidia conspicua (Diptera, Nycteribiidae) from Bulgaria (the first undoubtful country record), and on Penicillidia pachymela from Tanzania; Calvatia lilacina from Pakistan; Entoloma shangdongense from Pakistan; Erysiphe quercicola on Ziziphus jujuba (Rosales, Rhamnaceae) and E. urticae on Urtica dioica (Rosales, Urticaceae) from Pakistan; Fanniomyces ceratophorus on Fannia canicularis (Diptera, Faniidae) from the Netherlands; Marasmiellus biformis and M. subnuda from Pakistan; Morchella anatolica from Turkey; Ophiocordyceps ditmarii on Vespula vulgaris (Hymenoptera, Vespidae) from Austria; and Parvacoccum pini on Pinus cembra (Pinales, Pinaceae) from Austria. The new combinations are: Appendiculina gregaria, A. scaptomyzae, and Marasmiellus rodhallii. Analysis of an LSU dataset of Arthrorhynchus including isolates of A. eucampsipodae from Eucampsipoda africanum and Nycteribia spp. hosts, revealed that this taxon is a complex of multiple species segregated by host genus. Analysis of an SSU–LSU dataset of Laboulbeniomycetes sequences revealed support for the recognition of four monophyletic genera within Stigmatomyces sensu lato: Appendiculina, Fanniomyces, Gloeandromyces, and Stigmatomyces sensu stricto. Finally, phylogenetic analyses of Rhytismataceae based on ITS–LSU ribosomal DNA resulted in a close relationship of Parvacoccum pini with Coccomyces strobi.http://www.sydowia.at/index.htmpm2021Medical Virolog

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Antioxidants Attenuate Isolation- and L-DOPA-Induced Aggression in Mice

Aggression is a major hallmark worldwide attributing negative traits in personality. Wide variety of antioxidants is used for the treatment of many ailments. The present study was conducted to evaluate the role of antioxidants such as ascorbic acid (15.42 and 30.84 mg/kg), beta carotene (1.02 and 2.05 mg/kg), vitamin E (2.5 and 5.0 mg/kg), and N-acetyl cysteine (102.85 and 205.70 mg/kg) in the treatment of aggression. Two aggression models (isolation induced aggression model and L-DOPA induced aggression model) were used in the study. Male albino mice (n = 330) were used in the study which were further subdivided into 11 groups (Group I-control, group II-diseased, group III-standard group, group IV–V treated with ascorbic, group VI–VII treated with beta carotene, group VIII–IX treated with vitamin E, group X–XI treated with N-acetyl cysteine for 14 consecutive days). Different biochemical markers (glutathione, superoxide dismutase, and catalase) were determined to evaluate the antioxidant potential in oxidative stress. High dose of vitamin E (5.0 mg/kg) was more effective to reduce the aggression in isolated animals while all other antioxidants produced dose-dependent anti-aggressive effect except N-acetyl cysteine which had marked anti-aggressive effect at low dose (102.75 mg/kg). Low doses of vitamin E (2.5 mg/kg) and N-acetyl cysteine (102.75 mg/kg) and high dose of beta carotene (2.05 mg/kg) were effective to prevent all aggression parameters in acute anti-aggressive activity against L-DOPA induced aggression. However, all test antioxidants were equally effective in chronic anti-aggressive studies against L-DOPA induced aggression. It may be concluded that selected antioxidants can reverse the aggression which is a key symptom of many neurological disorder

Experimental and Computational Studies to Characterize and Evaluate the Therapeutic Effect of <i>Albizia lebbeck</i> (L.) Seeds in Alzheimer’s Disease

Background and Objectives: Alzheimer&#8217;s disease (AD) is a neurodegenerative disorder that deteriorates daily life due to loss of memory and cognitive impairment. It is believed that oxidative stress and cholinergic deficit are the leading causes of AD. Disease-modifying therapies for the treatment of AD are a challenging task for this century. The search for natural and synthetic agents has attracted the attention of researchers. The objective of this study was a scientific approach to search for most suitable remedy for AD by exploiting the potential of Albizia lebbeck (L.) seeds. Materials and Methods: Hydromethanolic extract of Albizia lebbeck seeds (ALE) was prepared by maceration. The plant was characterized by physico-chemical, phyto-chemical, and high-performance liquid chromatography (HPLC). Thirty-six Wistar albino rats were used in this study and divided into six groups (n = 6). Group I: normal control; Group II: disease control (AlCl3; 100 mg/kg); Group III: standard control (galantamine; 0.5 mg/kg); Groups IV&#8722;VI were treated ALE at 100, 200 and 300 mg/kg dose levels, respectively. All the treatments were given orally for 21 consecutive days. Y-maze, T-maze, Morris water maze, hole board, and open field behavioral tests were performed to analyze the cognitive impairment. Biochemical, histological, and computational studies were performed to support the results of behavioral tests. Results: HPLC analysis indicated the presence of quercetin, gallic acid, m-coumaric acid, and sinapic acid. ALE significantly improved the memory and cognitive impairments. Endogenous antioxidant stress biomarker levels and histopathological outcomes supported the therapeutic potential of A. lebbeck in AD. Cholinergic deficits were also ameliorated by ALE co-administration, possibly by the inhibition of hyperactive acetylcholinesterase (AChE). Docking studies supported the potential of ALE against AD. Conclusions: The data suggested that ALE has neuroprotective potential that can be exploited for beneficial effects to treat AD

Leucoagaricus fragilis sp. nov. (Agaricaceae) from Punjab, Pakistan

Niazi, Muhammad Asif Abdul Rehman, Izhar, Aiman, Khalid, Abdul Nasir, Bashir, Hira (2021): Leucoagaricus fragilis sp. nov. (Agaricaceae) from Punjab, Pakistan. Phytotaxa 501 (1): 140-150, DOI: 10.11646/phytotaxa.501.1.5, URL: http://dx.doi.org/10.11646/phytotaxa.501.1.

Cloning and expression analysis of alcohol dehydrogenase (Adh) hybrid promoter isolated from Zea mays

Hybrid promoters are created by shuffling of DNA fragments while keeping intact regulatory regions crucial of promoter activity. Two fragments of alcohol dehydrogenase (Adh) promoter from Zea mays were selected to generate hybrid promoter. Sequence analysis of both alcohol dehydrogenase promoter fragments through bioinformatics tools identified several crucial cis regulatory elements and transcription factors binding sites. Both fragments were separately cloned in the TA vector (pTZ57R/T) and fused to get the complete hybrid promoter (Adh-H). Alcohol dehydrogenase hybrid promoter was further cloned in expression vector pGR1 through adaptor ligation. Transient β-glucuronidase (GUS) assay revealed that hybrid promoter exhibited high expression under anaerobic conditions in wheat tissues. From the study it is concluded that hybrid promoter (Adh-H) may be used to derive gene expression in monocots during anaerobic conditions. The present work also provides an important insight in the designing of hybrid monocot promoters to improve multiple traits in crops without facing intellectual property rights (IPRs) issues.Key words: Hybrid promoter, histochemical β-glucuronidase (GUS) assay staining, cis regulatory elements, alcohol dehydrogenase, Zea mays