Exploring the chondroitin sulfate nanogel's potential in combating nephrotoxicity induced by cisplatin and doxorubicin-An in-vivo study on rats.

In this study, we aim to unveil the potential of itaconyl chondroitin sulfate nanogel (ICSNG) in tackling chronic kidney diseases triggered by the administration of CDDP and doxorubicin (Adriamycin, ADR). To that end, the new drug delivery system (ICSNG) was initially prepared, characterized, and loaded with the target drugs. Thereafter, the in-vivo studies were performed using five equally divided groups of 100 male Sprague-Dawley (SD) rats. Biochemical evaluation and immunohistochemistry studies have revealed the renal toxicity and the ameliorative effects of ICSNG on renal function. When ICSNG-based treatments were contrasted with the CDDP and ADR infected groups, they significantly increased paraoxonase-1 (PON-1), superoxide dismutase (SOD), catalase (CAT) and albumin activity and significantly decreased nitric oxide (NO), tumor necrosis factor alpha (TNF-α), creatinine, urea, and cyclooxygenase-2 (COX-2) activity (p < 0.001). The findings of the current study imply that ICSNG may be able to lessen renal inflammation and damage in chronic kidney disorders brought on by the administration of CDDP and ADR. Interestingly, according to the estimated selectivity indices, the ICSNG-encapsulated drugs have demonstrated superior selectivity for cancer MCF-7 cells, over healthy HSF cells, in comparison to the bare drugs.

Ultrasensitive Visual Tracking of Toxic Cyanide Ions in Biological Samples Using Biocompatible Metal-Organic Frameworks Architectures.

The extraordinary accumulation of cyanide ions within biological cells is a severe health risk. Detecting and tracking toxic cyanide ions within these cells by simple and ultrasensitive methodologies are of immense curiosity. Here, continuous tracking of ultimate levels of CN--ions in HeLa cells was reported employing biocompatible branching molecular architectures (BMAs). These BMAs were engineered by decorating colorant-laden dendritic branch within and around the molecular building hollows of the geode-shelled nanorods of organic-inorganic Al-frameworks. Batch-contact methods were utilized to assess the potential of hollow-nest architecture for inhibition/evaluation of toxicant CN--ions within HeLa cells. The nanorod BMAs revealed significant potential capabilities in monitoring and tracking of CN- ions (88 parts per trillion) in biological trials within seconds. These results demonstrated sufficient evidence for the compatibility of BMAs during HeLa cell exposure. Under specific conditions, the BMAs were utilized for in-vitro fluorescence tracking/sensing of CN- in HeLa cells. The cliff swallow nest with massive mouths may have the potential to reduce the health hazards associated with toxicant exposure in biological cells.

Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus.

Antagonistic bacterial interactions often rely on antimicrobial bacteriocins, which attack only a narrow range of target bacteria. However, antimicrobials with broader activity may be advantageous. Here we identify an antimicrobial called epifadin, which is produced by nasal Staphylococcus epidermidis IVK83. It has an unprecedented architecture consisting of a non-ribosomally synthesized peptide, a polyketide component and a terminal modified amino acid moiety. Epifadin combines a wide antimicrobial target spectrum with a short life span of only a few hours. It is highly unstable under in vivo-like conditions, potentially as a means to limit collateral damage of bacterial mutualists. However, Staphylococcus aureus is eliminated by epifadin-producing S. epidermidis during co-cultivation in vitro and in vivo, indicating that epifadin-producing commensals could help prevent nasal S. aureus carriage. These insights into a microbiome-derived, previously unknown antimicrobial compound class suggest that limiting the half-life of an antimicrobial may help to balance its beneficial and detrimental activities.

Chemotherapeutic Activity of Imidazolium-Supported Pd(II) o-Vanillylidene Diaminocyclohexane Complexes Immobilized in Nanolipid as Inhibitors for HER2/neu and FGFR2/FGF2 Axis Overexpression in Breast Cancer Cells.

Two bis-(imidazolium-vanillylidene)-(R,R)-diaminocyclohexane ligands (H2(VAN)2dach, H2L1,2) and their Pd(II) complexes (PdL1 and PdL2) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL1LNP and PdL2LNP), which are physicochemically and morphologically characterized. PdL1LNP and PdL2LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL1LNP and PdL2LNP to downregulate TGFß1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions.

Knowledge and Awareness About Food Allergy Among Mothers With Allergic Children in the Aseer Region, Saudi Arabia.

Introduction Food allergies have become a significant health concern worldwide, affecting individuals of all age groups. It is particularly challenging for parents who have children diagnosed with food allergies, as they bear the responsibility of managing their child's condition and ensuring their safety. This study aimed to assess the knowledge and awareness about food allergies among mothers with allergic children in the Aseer region, Saudi Arabia. Methodology A cross-sectional study design was employed, and data were collected through a structured questionnaire administered to 400 mothers. The participants were selected through convenience sampling. Descriptive statistics, including frequencies and percentages, were used to summarize the demographic characteristics, knowledge and awareness levels, prevalence of allergenic foods, manifestations of food allergies, and factors influencing food allergies. Chi-squared tests were conducted to assess associations between variables. Results The study revealed a balanced representation across different age groups among the surveyed mothers, with the highest proportion falling in the 31-40 years range. A significant proportion of mothers had a university education, indicating a relatively higher level of education among the participants. The majority of mothers were employed in governmental positions, followed by housewives and those working in the private sector. Regarding knowledge and awareness, a substantial percentage of mothers correctly identified key aspects of food allergies. However, knowledge gaps were observed, particularly in understanding the hereditary nature. The prevalence of allergenic foods varied, with seafood (fish, shrimp, and tuna) emerging as the most commonly reported allergenic foods, followed by eggs, milk, wheat, chocolate, fruits, nuts, and other food types. Manifestations associated with food allergies were reported, including skin, respiratory, eye, nasal, gastrointestinal, and other symptoms. The associations between different feeding methods and the occurrence of medically diagnosed food allergies were found to be non-significant. However, having other children with food allergies showed a highly significant association with the occurrence of food allergies in the current child. The age of introducing solid food did not demonstrate a significant association with the occurrence of food allergies. Conclusion This study provides insights into the knowledge and awareness about food allergies among mothers with allergic children in the Aseer region, Saudi Arabia. While mothers demonstrated a reasonable understanding of food allergies, knowledge gaps were identified, particularly regarding the hereditary nature. The prevalence of allergenic foods aligns with previous studies, although variations across populations should be considered. The manifestations reported by the participants corroborate known allergic reactions, necessitating further analysis.

Bis(pyridine)enaminone as a Precursor for the Synthesis of Bis(azoles) and Bis(azine) Utilizing Recent Economic Green Chemistry Technology: The Q-Tube System.

We reported herein efficient economic high-pressure synthesis procedures for the synthesis of bis(azoles) and bis(azines) by utilizing the bis(enaminone) intermediate. Bis(enaminone) reacted with hydrazine hydrate, hydroxylamine hydrochloride, guanidine hydrochloride, urea, thiourea, and malononitrile to form the desired bis azines and bis azoles. A combination of elemental analyses and spectral data was used to confirm the structures of the products. Compared with conventional heating, the high-pressure Q-Tube method promotes reactions in a short period of time and provides high yields.

A Systematic Review and Meta-analysis of the Prevalence and Risk Factors in Cardiac Implantable Electronic Device Malfunction.

Introduction: Cardiac implantable electronic devices (CIED) include permanent pacemakers (PPMs), implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. They treat several cardiac issues and are dependent on batteries; however, similar to any medical equipment, they can fail. The prevalence and risk factors for CIED malfunction must be understood for earlier detection and better patient outcomes. Material and methods: A comprehensive search was conducted through electronic bibliographic sources (PubMed and Cochrane) until January 2023 in order to identify reviews, cohort studies and case reports pertaining to CIED. The primary outcome is the probability of CIED malfunction. The secondary outcome concerned significant risk factors. Two authors independently extracted articles by utilizing pre-established data fields. Using a random-effects model, the aggregated prevalence and 95 % confidence intervals (CIs) were computed. Results: The meta-analysis comprised eight review articles, twenty-two retrospective studies, and thirty-seven case reports from the systematic review. The eight review articles contained a CIED malfunction of 4.03 % (random-effects model). The pooled prevalence of CIED malfunction in the meta-analysis of 22 retrospective studies was 0.41 percent (using a fixed-effects model) and 8.01 percent (using a random-effects model). Moreover, age, pre-existing cardiac conditions, CIED type, lead placement, and medical device interactions all contributed to an increase in the heterogeneity (I2 = 98.90 %) of the risk of CIED malfunction. Conclusion: CIED malfunction is common and more likely to occur in elderly individuals and in certain types of CIED. Clinicians should focus on risk factors and closely monitor the patients with higher probability for CIED malfunction with short intervals.

A Systematic Review Evaluating the Effectiveness of Several Biological Therapies for the Treatment of Skin Psoriasis.

Psoriasis is a chronic inflammatory skin illness that has the potential to manifest at any stage of life, it is most frequently observed in early adulthood. Biological drugs have significantly transformed the landscape of psoriasis treatment through the provision of focused therapy, which effectively mitigates inflammation and regulates the overproduction of skin cells. Notwithstanding the accessibility of these biological drugs, rigorous evaluations that juxtapose their safety and efficacy profiles are necessary. The objective of this study is to conduct a thorough investigation of the relative efficacy of these drugs in alleviating psoriasis symptoms and increasing the quality of life for patients by synthesizing the existing evidence. A comprehensive review was conducted to evaluate and compare the safety and effectiveness of different biochemical medicines utilized in the management of psoriasis. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, the review process was conducted among the available studies. A search was conducted across electronic databases, such as Web of Science, PubMed, and Embase, utilizing a combination of keywords and Mesh phrases pertaining to psoriasis, biological medications, and particular names of pharmaceuticals. In total, 475 studies were ascertained by the preliminary search of the database. After eliminating duplicate research, 358 distinct studies remained. After meticulous screening of titles and abstracts against the predefined inclusion criteria, 281 papers were deemed ineligible and thus excluded. For final inclusion, the whole texts of the remaining 77 studies were evaluated. Forty additional papers were removed during the full-text evaluation for a variety of reasons, including improper research design, or insufficient outcome data. Finally, 37 studies were included in this systematic review since they satisfied all inclusion criteria. The results of the current systematic review showed that all biological medications showed high efficacy in the treatment of skin psoriasis compared with placebo based on the clinical assessment outcomes using different tools such as PASI.

Bioactive Inorganic Materials for Dental Applications: A Narrative Review.

Over time, much attention has been given to the use of bioceramics for biomedical applications; however, the recent trend has been gaining traction to apply these materials for dental restorations. The bioceramics (mainly bioactive) are exceptionally biocompatible and possess excellent bioactive and biological properties due to their similar chemical composition to human hard tissues. However, concern has been noticed related to their mechanical properties. All dental materials based on bioactive materials must be biocompatible, long-lasting, mechanically strong enough to bear the masticatory and functional load, wear-resistant, easily manipulated, and implanted. This review article presents the basic structure, properties, and dental applications of different bioactive materials i.e., amorphous calcium phosphate, hydroxyapatite, tri-calcium phosphate, mono-calcium phosphate, calcium silicate, and bioactive glass. The advantageous properties and limitations of these materials are also discussed. In the end, future directions and proposals are given to improve the physical and mechanical properties of bioactive materials-based dental materials.

Desert soil fungi isolated from Saudi Arabia: cultivable fungal community and biochemical production.

Desert soils harbor fungi that have survived under highly stressed conditions of high temperature and little available moisture. This study was designed to survey the communities of cultivable fungi in the desert soils of the Arabian Peninsula and to screen the fungi for the potentially valuable antioxidants (flavonoids, phenols, saponins, steroids, tannins, terpenoids, and alkaloids) and enzymes (cellulase, laccase, lipase, protease, amylase, and chitinase). Desert soil was sampled at 30 localities representing different areas of Saudi Arabia and studied for physico-chemical soil properties. Five types of soil texture (sand, loamy sand, sandy loam, silty loam, and sandy clay loam) were observed. A total of 25 saprotrophic species was identified molecularly from 68 isolates. Our survey revealed 13 culturable fungal species that have not been reported previously from Arabian desert soils and six more species not reported from Saudi Arabian desert soils. The most commonly recorded genera were Aspergillus (isolated from 20 localities) and Penicillium (6 localities). The measurements of biochemicals revealed that antioxidants were produced by 49 and enzymes by 52 isolates; only six isolates did not produce any biochemicals. The highest biochemical activity was observed for the isolates Fusarium brachygibbosum and A. phoenicis. Other active isolates were A. proliferans and P. chrysogenum. The same species, for instance, A. niger had isolates of both high and low biochemical activities. Principal component analysis gave a tentative indication of a relationship between the biochemical activity of fungi isolated from soil and soil texture variables namely the content of silt, clay and sand. However, any generalizable relation between soil properties and fungal biochemical activities cannot be suggested. Each fungal isolate is probable to produce several antioxidants and enzymes, as shown by the correlation within the compound groups. Desert soil warrants further research as a promising source of biochemicals.

Incidence, Knowledge, Attitude and Practice Toward Needle Stick Injury Among Health Care Workers in Abha City, Saudi Arabia.

BACKGROUND: A needle stick injury is a serious occupational health hazard in health care settings. Health care workers are at risk of bloodborne diseases and the psychological consequences of these injuries. This study aims to estimate the incidence of needle stick injuries among healthcare workers during the previous 12 months and to assess their knowledge, attitude, and practice toward these injuries. METHODS: This cross-sectional study was conducted from 1st August 2019 till 15th February 2020, and included 786 healthcare workers in Abha city, Saudi Arabia. A structured questionnaire was used to collect the data. RESULTS: The incidence of needle stick injury among healthcare workers during the previous 12 months was (91/786) 11.57%. Nurses, females, and Saudis reported most needle stick injuries. More than half (52.7%) of the injuries went unreported. About 52.7% of needle stick injuries occurred during using sharp devices, and 42.9% of injuries happened in the patient room. The incidence of needle stick injury was significantly higher among those working at the secondary healthcare level (p = 0.003) and those practicing surgery (p < 0.001). Out of 786 participants, 94.7% knew the definition of needle stick injury, and 81.0% were aware of the procedure and guidelines to follow on sustaining a needle stick injury. Only 61.2% recognized that the recap of the needle is not recommended. Almost half of the participants (47.1%) agreed, and 33.6% strongly agreed that needle stick injury is preventable. A majority of healthcare workers (89.1%) had been vaccinated against Hepatitis B. Nearly 27.5% of healthcare workers incorrectly practiced recapping the needles with two hands and 8.7% bent needles before disposal. Recapping the needles was statistically significantly higher among healthcare workers who had a history of needle stick injury (p = 0. 046). CONCLUSION: Needle stick injury and its under reporting among healthcare professionals is still a prevalent risk. Raising awareness among healthcare workers and improving the reporting systems for needle stick injuries to ensure more protection and early use of post-exposure prophylaxis is required. Implementation of safety precautions and safe injection practices and providing engineered safety devices may further reduce the risk.

Association between Periodontal Disease and Comorbidities in Saudi's Eastern Province.

The incidence of periodontal diseases is associated with multiple comorbidities that influence a patient's treatment planning. This study evaluates the relation between periodontal disease and multiple comorbidities reported in the Saudi population from the Eastern province. This study was conducted on 190 patients, who visited the periodontology clinics at Imam Abdulrahman Bin Faisal University, Saudi Arabia. Demographic data, smoking habits, past medical and dental histories, blood pressure, random blood glucose, and recent haemoglobin A1c were recorded. A comprehensive periodontal examination included the number of missing teeth, pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and mobility of all teeth except third molars. Radiographic bone loss was measured on standardized full-mouth periapical radiographs. Multivariable regression models were calculated aiming to see the association between different comorbidities and alveolar bone loss with confounders controlled. Out of 190 periodontitis patients, 56 (29.5%) were males and 134 (70.5%) were females. More than half of the patients (60%) were between 26 and 50 years, 30% of them had diabetes, and 18% were smokers. The risk of alveolar bone loss was higher in persons who had diabetes and those who had both diabetes and coronary heart disease than those who did not, although the association was not statistically significant (B = 1.26, 95%CI = -0.30, 2.82, and B = 2.86, 95%CI = -1.25, 6.96, respectively). The risk of alveolar bone loss was significantly higher among persons with diabetes and hypertension (B = 2.82 and 95%CI = 0.89, 4.75). Collectively, the risk of alveolar bone loss in periodontitis patients increases with diabetes in the presence of other comorbidities regardless of smoking or gender.

Comparison of microleakage between different restorative materials to restore marginal gap at crown margin.

BACKGROUND: An occurrence of secondary caries around the indirect restoration margin is reported to remain a leading cause of failures. OBJECTIVE: This study aimed to test the interfacial microleakage of conventional glass-ionomer (CGI), resin-modified glass ionomer (RMGI) and Nano-hybrid composite (CR) restorations at a full veneer margin crown. METHODS: Ninety human extracted molar teeth were divided into three groups (n = 30). Each group was subdivided into three subgroups (n = 10) according to the extent of the structural defects; The structural defect in G1 had a depth of 1.5 mm, width and length at 2 mm and 1 mm intrusion within the crown cervical margin. The corresponding structural defect dimension values for G2 were 2, 5, 4 and 2 mm with defects extending onto the root structure. Meanwhile, G3: structural deficiency of 2 mm depth, 3 mm width and 3 mm length and with 1.5 mm extension into the prepared teeth. These structural defects in each subgroup were restored with CGI, RMGI and CR. Artificial carious lesion formation was induced at the cervical finish line with a demineralizing solution. The artificial carious lesions were restored as per the group distribution. Subsequently, teeth samples were prepared and cemented with Nickel-chromium full coverage restorations utilizing glass-ionomer luting cement. Teeth samples were thermocycled, isolated with nail varnish, and immersed in 0.1% methylene blue for 24 h. The teeth samples were sectioned longitudinally, dye penetration was evaluated with a stereomicroscope. The data were analyzed with Kruskal-Wallis and Mann-Whitney U tests. RESULTS: CGI-G1 recorded the highest micro-leakage score at 1.450; while CR-G3 recorded the least score (0.350). At a cementum-restoration interface, CR-G1 (0.850) documented the lowest micro-leakage; RMGI-G3 had a greater value at 1.700. CONCLUSIONS: The hybrid CR could be effectively used to restore the restoration of a marginal gap around crown margins.

Quantifying Triplet State Formation in Zinc Dipyrrin Complexes.

Photocatalysis is a promising method to harness solar energy and use it to form fuels and other high-value chemicals, but most sensitizers used in photocatalytic reactions are complexes of rare and expensive metals such as ruthenium and iridium. Zinc dipyrromethene complexes have potential to be a more earth-abundant alternative, but their photophysical properties are largely unexplored. In this study, triplet state formation was quantified in two zinc dipyrromethene complexes, with and without heavy atoms, by transient absorption spectroscopy. Without heavy atoms, the triplet quantum yield was 16% in toluene and 27% in THF. With the addition of heavy I atoms, the triplet quantum yield increased to 62-63% and was insensitive to solvent polarity. The fact that in the absence of heavy atoms the triplet yield is affected by solvent polarity and in the presence of heavy atoms it is not suggests that triplet formation occurs through different pathways in the two complexes. These triplet yields meet or exceed those of successful organic photosensitizers, illustrating the potential for zinc dipyrromethene complexes as photosensitizers.

Multi Component Reactions under Increased Pressure: On the Mechanism of Formation of Pyridazino[5,4,3-de][1,6]naphthyridine Derivatives by the Reaction of Malononitrile, Aldehydes and 2-Oxoglyoxalarylhydrazones in Q-Tubes.

Efficient synthesis of phenanthridin-6(5H)-one derivatives 12a-n in a four-component reaction of aldehyde hydrazone, aromatic aldehydes and malononitrile in Q-Tubes is reported. The results showed that the methodology has the advantage of being a one-pot synthesis of tricyclic systems in good yields. Potential routes leading to formation of compounds 12 are discussed. The structures of the synthesized compounds could be unequivocally established via X-ray crystal structure determination and spectroscopic methods.

Two Distinct Cyclodipeptide Synthases from a Marine Actinomycete Catalyze Biosynthesis of the Same Diketopiperazine Natural Product.

Diketopiperazine natural products are structurally diverse and offer many biological activities. Cyclodipeptide synthases (CDPSs) were recently unveiled as a novel enzyme family that employs aminoacyl-tRNAs as substrates for 2,5-diketopiperazine assembly. Here, the Nocardiopsis sp. CMB-M0232 genome is predicted to encode two CDPSs, NozA and NcdA. Metabolite profiles from E. coli expressing these genes and assays with purified recombinant enzymes revealed that NozA and NcdA catalyze cyclo(l-Trp-l-Trp) (1) biosynthesis from tryptophanyl-tRNA and do not accept other aromatic aminoacyl-tRNA substrates. Fidelity is uncommon among characterized CDPSs, making NozA and NcdA important CDPS family additions. Further, 1 was previously supported as a biosynthetic precursor of the nocardioazines; the current study suggests that Nocardiopsis sp. may derive this precursor from both NozA and NcdA. This study offers a rare example of a single bacterium encoding multiple phylogenetically distinct enzymes that yield the same secondary metabolite and provides tools for chemoenzymatic syntheses of indole alkaloid diketopiperazines.

The sensitivity, specificity, predictive values, and likelihood ratios of fecal occult blood test for the detection of colorectal cancer in hospital settings.

OBJECTIVES: To study the performance of a single test using two fecal occult blood tests with colonoscopy for the detection of colorectal cancer (CRC) for the first time in Saudi Arabia to determine possible implications for the anticipated colorectal screening program. MATERIALS AND METHODS: We compared the performance of guaiac and immunochemical fecal occult blood tests for the detection of CRC among patients of 50-74 years old attending two hospitals in the Eastern Region of Saudi Arabia. Samples of feces were collected from 257 asymptomatic patients and 20 cases of confirmed CRC, and they were tested simultaneously by the guaiac-based occult blood test and monoclonal antibody-based immunoassay kit. Colonoscopy was performed on all participants and the results were statistically analyzed with both positive and negative occult blood tests of both methods. RESULTS: Of the 277 subjects, 79 tested positive for occult blood with at least one method. Overall, the number of those with an occult blood-positive result by both tests was 39 (14.1%), while for 198 (71.5%), both tests were negative (P<0.0001); 40 (14.4%) samples showed a discrepant result. Colonoscopy data were obtained for all 277 patients. A total of three invasive cancers were detected among the screening group. Of the three, the guaiac test detected two cases, while the immunochemical test detected three of them. Of the 20 control cases, the guaiac test detected 13 CRC cases (P=0.03), while the immunochemical test detected 16 of them (P<0.0001). The sensitivity of guaiac and immunochemical tests for the detection of CRC in the screening group was 50.00% (95% confidence interval [CI] =6.76-93.24) and 75.00% (95% CI =19.41-99.37), respectively. For comparison, the sensitivity of the guaiac fecal occult blood test for detecting CRC among the control group was 65.00% (95% CI =40.78-84.61) while that of FIT was 80.00% (95% CI =56.34-94.27). The specificity of the guaiac and immunoassay tests was 77.87% (95% CI =72.24-82.83) and 90.12% (95% CI =85.76-93.50), respectively. The positive likelihood ratio of guaiac and immunochemical tests for the detection of CRC was 2.26 (95% CI =0.83-6.18) and 7.59 (95% CI =3.86-14.94), whereas the negative likelihood ratio was 0.64 (95% CI =0.24-1.71) and 0.28 (95% CI =0.05-1.52), respectively. The positive predictive values of guaiac and immunochemical tests were 3.45% (95% CI =0.426-11.91) and 10.71% (95% CI =2.27-28.23), respectively. There was no marked difference in the negative predictive values for both methods. The sensitivity of the fecal occult blood test by FIT was significantly higher for stages III and IV colorectal cancer than for stages I and II (P=0.01) and it was insignificant for the guaiac fecal occult blood test (P=0.07). CONCLUSION: In areas where other advance screening methods of CRC are not feasible, the use of FIT can be considered.

Correction: Synergism between genome sequencing, tandem mass spectrometry and bio-inspired synthesis reveals insights into nocardioazine B biogenesis.

Correction for 'Synergism between genome sequencing, tandem mass spectrometry and bio-inspired synthesis reveals insights into nocardioazine B biogenesis' by Norah Alqahtani et al., Org. Biomol. Chem., 2015, 13, 7177-7192.

Synergism between genome sequencing, tandem mass spectrometry and bio-inspired synthesis reveals insights into nocardioazine B biogenesis.

Marine actinomycete-derived natural products continue to inspire chemical and biological investigations. Nocardioazines A and B (3 and 4), from Nocardiopsis sp. CMB-M0232, are structurally unique alkaloids featuring a 2,5-diketopiperazine (DKP) core functionalized with indole C3-prenyl as well as indole C3- and N-methyl groups. The logic of their assembly remains cryptic. Bioinformatics analyses of the Nocardiopsis sp. CMB-M0232 draft genome afforded the noz cluster, split across two regions of the genome, and encoding putative open reading frames with roles in nocardioazine biosynthesis, including cyclodipeptide synthase (CDPS), prenyltransferase, methyltransferase, and cytochrome P450 homologs. Heterologous expression of a twelve gene contig from the noz cluster in Streptomyces coelicolor resulted in accumulation of cyclo-l-Trp-l-Trp DKP (5). This experimentally connected the noz cluster to indole alkaloid natural product biosynthesis. Results from bioinformatics analyses of the noz pathway along with challenges in actinomycete genetics prompted us to use asymmetric synthesis and mass spectrometry to determine biosynthetic intermediates in the noz pathway. The structures of hypothesized biosynthetic intermediates 5 and 12-17 were firmly established through chemical synthesis. LC-MS and MS-MS comparison of these synthetic compounds with metabolites present in chemical extracts from Nocardiopsis sp. CMB-M0232 revealed which of these hypothesized intermediates were relevant in the nocardioazine biosynthetic pathway. This established the early and mid-stages of the biosynthetic pathway, demonstrating that Nocardiopsis performs indole C3-methylation prior to indole C3-normal prenylation and indole N1'-methylation in nocardioazine B assembly. These results highlight the utility of merging bioinformatics analyses, asymmetric synthetic approaches, and mass spectrometric metabolite profiling in probing natural product biosynthesis.

Characterization of the nocardiopsin biosynthetic gene cluster reveals similarities to and differences from the rapamycin and FK-506 pathways.

Macrolide-pipecolate natural products, such as rapamycin (1) and FK-506 (2), are renowned modulators of FK506-binding proteins (FKBPs). The nocardiopsins, from Nocardiopsis sp. CMB-M0232, are the newest members of this structural class. Here, the biosynthetic pathway for nocardiopsins A-D (4-7) is revealed by cloning, sequencing, and bioinformatic analyses of the nsn gene cluster. In vitro evaluation of recombinant NsnL revealed that this lysine cyclodeaminase catalyzes the conversion of L-lysine into the L-pipecolic acid incorporated into 4 and 5. Bioinformatic analyses supported the conjecture that a linear nocardiopsin precursor is equipped with the hydroxy group required for macrolide closure in a previously unobserved manner by employing a P450 epoxidase (NsnF) and limonene epoxide hydrolase homologue (NsnG). The nsn cluster also encodes candidates for tetrahydrofuran group biosynthesis. The nocardiopsin pathway provides opportunities for engineering of FKBP-binding metabolites and for probing new enzymology in nature's polyketide tailoring arsenal.