Inhibition of cancer cells by Quinoline-Based compounds: A review with mechanistic insights.

This article includes a thorough examination of the inhibitory potential of quinoline-based drugs on cancer cells, as well as an explanation of their modes of action. Quinoline derivatives, due to their various chemical structures and biological activity, have emerged as interesting candidates in the search for new anticancer drugs. The review paper delves into the numerous effects of quinoline-based chemicals in cancer progression, including apoptosis induction, cell cycle modification, and interference with tumor-growth signaling pathways. Mechanistic insights on quinoline derivative interactions with biological targets enlightens their therapeutic potential. However, obstacles such as poor bioavailability, possible off-target effects, and resistance mechanisms make it difficult to get these molecules from benchside to bedside. Addressing these difficulties might be critical for realizing the full therapeutic potential of quinoline-based drugs in cancer treatment.

Synthesis of fused polycyclic ß-carboline derivatives using Ugi-4CR followed by cascade cyclization.

Ugi-four component reaction (Ugi-4CR) is extremely attractive for diversity-oriented and step economical synthesis as evident from past applications. Here we report the synthesis of fused polycyclic ß-carboline derivatives by sequential Pictet-Spengler's and Ugi-4CR multi-component reaction followed by cascade cyclization. The post cyclisation of Ugi product provides conformationally stable heterocyclic molecule that is expected to be suitable for interaction with different biological targets. The methodology provides a simple and facile access to heterocycles embedded in polycyclic framework which otherwise seems difficult to synthesize by conventional methods. Synthesis of fused Polycyclic ß-Carboline Derivatives Using Ugi-4CR Followed by Cascade Cyclization.

Microbial Journey: Mount Everest to Mars.

A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis.

BACKGROUND: Data on the effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in reducing cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD) are limited. We investigated the association between ACEI/ARB use and CV outcomes in patients initiating PD. METHODS: In this observational cohort study, we identified from the United States Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We applied Cox regression to an inverse probability of treatment weighted cohort to estimate the hazard ratios (HRs) for the combined outcome of death, ischemic stroke or myocardial infarction (MI) and each outcome individually. RESULTS: Among 4879 patients, 2063 (42%) used an ACEI/ARB. Patients were followed up for a median of 1.2 years. We recorded 1771 events, for a composite rate of 25 events per 100 person-years. ACEI/ARB use (versus nonuse) was associated with a reduced risk of the composite outcome {HR 0.84 [95% confidence interval (CI) 0.76-0.93]}, all-cause mortality [HR 0.83 (95% CI 0.75-0.92)] and CV death [HR 0.74 (95% CI 0.63-0.87)], but not MI [HR 0.88 (95% CI 0.69-1.12)] or ischemic stroke [HR 1.06 (95% CI 0.79-1.43)]. Results were similar in as-treated analyses. In a subgroup analysis, we did not find any effect modification by residual renal function. CONCLUSIONS: ACEI/ARB use is common in patients initiating PD and is associated with a lower risk of fatal CV outcomes.

Renin-angiotensin system blockers and residual kidney function loss in patients initiating peritoneal dialysis: an observational cohort study.

BACKGROUND: Although angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U.S. METHODS: We conducted a retrospective observational cohort study using the US Renal Data System and electronic health records data from a large national dialysis provider. We identified adult patients who initiated PD from 2007 to 2011. Only patients who participated in the federal prescription drug benefit program, Medicare Part D, for the first 90 days of dialysis were included. Patients who filled a prescription for an ACEI or ARB during those 90 days were considered users. We applied Cox proportional hazards models to an inverse probability of treatment-weighted (IPTW) cohort to estimate the hazard ratio (HR) for anuria (24-h urine volume < 200 ml) in ACEI/ARB users vs. non-users. RESULTS: Among 886 patients, 389 (44%) used an ACEI/ARB. Almost a third of these patients were black or Hispanic, and more than a quarter had comorbidities that would have excluded them from the randomized clinical trials of ACEI/ARB. Two hundred eighty patients reached anuria over 840 person-years of follow-up, for a composite event rate of 33 events per 100 person-years. We found no clear association between ACEI/ARB use and progression to anuria [HR: 0.86, 95% CI: 0.73-1.02]. CONCLUSIONS: ACEI/ARB use is common in patients initiating PD in the U.S. but was not associated with a lower risk of anuria. Residual confounding by unmeasured variables is an important limitation of this observational study. Still, these findings suggest that pragmatic clinical trials are warranted to test the effectiveness of ACEI/ARB in slowing the decline of residual kidney function in a diverse population of peritoneal dialysis patients with multiple comorbid conditions.

Comparison of efficacy of cell block versus conventional smear study in exudative fluids.

INTRODUCTION: Cytological examination of serous effusions helps in staging, prognostication and management of patients with malignancy. The method has disadvantage of lower sensitivity in differentiating reactive atypical mesothelial cells from malignant cells. AIM: The aim of this study is to compare the cytological features of pleural and peritoneal exudative fluids by conventional smear (CS) method and cell block (CB) method and also to assess the utility of a combined approach for cytodiagnosis of these effusions. MATERIALS AND METHODS: One hundred and fifty-three pleural and peritoneal exudative fluid samples were subjected to evaluation by both CS and CB methods over a period of 2 years. Cellularity, architecture patterns, morphological features and yield for malignancy were compared, using the two methods. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for diagnosing malignancy were calculated by both methods, using histology as a gold standard. RESULTS: CB method provided higher cellularity, better architectural patterns and additional yield for malignancy as compared to CS method (P < 0.005). Sensitivity, specificity, PPV, NPV, and accuracy by CS method were 69.2%, 95%, 56.25%, 97.08% and 92.8%, while by CB method were 92.30%, 99.2%, 92.30%, 99.28% and 98.6%. CONCLUSION: The present study shows that it is advisable to routinely make CBs before discarding specimens that are suspicious for malignancy by smear examination.

Laboratory and field scale bioremediation of hexachlorocyclohexane (HCH) contaminated soils by means of bioaugmentation and biostimulation.

Hexachlorocyclohexane (HCH) contaminated soils were treated for a period of up to 64 days in situ (HCH dumpsite, Lucknow) and ex situ (University of Delhi) in line with three bioremediation approaches. The first approach, biostimulation, involved addition of ammonium phosphate and molasses, while the second approach, bioaugmentation, involved addition of a microbial consortium consisting of a group of HCH-degrading sphingomonads that were isolated from HCH contaminated sites. The third approach involved a combination of biostimulation and bioaugmentation. The efficiency of the consortium was investigated in laboratory scale experiments, in a pot scale study, and in a full-scale field trial. It turned out that the approach of combining biostimulation and bioaugmentation was most effective in achieving reduction in the levels of α- and ß-HCH and that the application of a bacterial consortium as compared to the action of a single HCH-degrading bacterial strain was more successful. Although further degradation of ß- and δ-tetrachlorocyclohexane-1,4-diol, the terminal metabolites of ß- and δ-HCH, respectively, did not occur by the strains comprising the consortium, these metabolites turned out to be less toxic than the parental HCH isomers.

Modification of rifamycin polyketide backbone leads to improved drug activity against rifampicin-resistant Mycobacterium tuberculosis.

Rifamycin B, a product of Amycolatopsis mediterranei S699, is the precursor of clinically used antibiotics that are effective against tuberculosis, leprosy, and AIDS-related mycobacterial infections. However, prolonged usage of these antibiotics has resulted in the emergence of rifamycin-resistant strains of Mycobacterium tuberculosis. As part of our effort to generate better analogs of rifamycin, we substituted the acyltransferase domain of module 6 of rifamycin polyketide synthase with that of module 2 of rapamycin polyketide synthase. The resulting mutants (rifAT6::rapAT2) of A. mediterranei S699 produced new rifamycin analogs, 24-desmethylrifamycin B and 24-desmethylrifamycin SV, which contained modification in the polyketide backbone. 24-Desmethylrifamycin B was then converted to 24-desmethylrifamycin S, whose structure was confirmed by MS, NMR, and X-ray crystallography. Subsequently, 24-desmethylrifamycin S was converted to 24-desmethylrifampicin, which showed excellent antibacterial activity against several rifampicin-resistant M. tuberculosis strains.

Urgent-start peritoneal dialysis: a chance for a new beginning.

Peritoneal dialysis (PD) remains greatly underutilized in the United States despite the widespread preference of home modalities among nephrologists and patients. A hemodialysis-centric model of end-stage renal disease care has perpetuated for decades due to a complex set of factors, including late end-stage renal disease referrals and patients who present to the hospital requiring urgent renal replacement therapy. In such situations, PD rarely is a consideration and patients are dialyzed through a central venous catheter, a practice associated with high infection and mortality rates. Recently, the term urgent-start PD has gained momentum across the nephrology community and has begun to change this status quo. It allows for expedited placement of a PD catheter and initiation of PD therapy within days. Several published case reports, abstracts, and poster presentations at national meetings have documented the initial success of urgent-start PD programs. From a wide experiential base, we discuss the multifaceted issues related to urgent-start PD implementation, methods to overcome barriers to therapy, and the potential impact of this technique to change the existing dialysis paradigm.

Synthetic Biology in Action: Developing a Drug Against MDR-TB.

The amalgamation of the research efforts of biologists, chemists and geneticists led by scientists at the Department of Zoology, University of Delhi has resulted in the development of a novel rifamycin derivative; 24-desmethylrifampicin, which is highly effective against multi-drug resistant (MDR) strains of Mycobacterium tuberculosis. The production of rifamycin analogue was facilitated by genetic-synthetic strategies that have opened an interdisciplinary route for the development of more such rifamycin analogues aiming at a better therapeutic potential. The results of this painstaking effort of nearly 25 years of a team of students and scientists led by Professor Rup Lal have been recently published in the Journal of Biological Chemistry (www.jbc.org/content/289/30/21142.long). This strategy can now find applications for developing newer rifamycin analogues that can be harnessed to overcome the problem of MDR, extensively drug resistant (XDR) and totally drug resistant (TDR) M. tuberculosis.

Novosphingobium lindaniclasticum sp. nov., a hexachlorocyclohexane (HCH)-degrading bacterium isolated from an HCH dumpsite.

A yellow-pigmented, Gram-negative, aerobic, non-motile, non-spore-forming, rod-shaped-bacterium, LE124(T), was isolated from a hexachlorocyclohexane (HCH) dumpsite located in Lucknow, India. The type strain LE124(T) grew well with hexachlorocyclohexane as a sole carbon source, degrading it within 24 h of incubation. Phylogenetic analysis of strain LE124(T) showed highest 16S rRNA gene sequence similarity to Novosphingobium barchaimii LL02(T) (98.5%), Novosphingobium panipatense SM16(T) (98.1%), Novosphingobium soli CC-TPE-1(T) (97.9%), Novosphingobium naphthalenivorans TUT562(T) (97.6%), Novosphingobium mathurense SM117(T) (97.5%) and Novosphingobium resinovorum NCIMB 8767(T) (97.5%) and lower sequence similarity (<97%) to all other members of the genus Novosphingobium. The DNA-DNA relatedness between strain LE124(T) and N. barchaimii LL02(T) and other related type strains was found to vary from 15% to 45% confirming that it represents a novel species. The genomic DNA G+C content of strain LE124(T) was 60.7 mol%. The predominant fatty acids were summed feature 8 (C18:1ω7c, 49.1%), summed feature 3 (C16:1ω7c/C16:1ω6c, 19.9%), C16:0 (6.7%), C17:1ω6c (4.9%) and a few hydroxyl fatty acids, C14:0 2-OH (9.4%) and C16:0 2-OH (2.1%). Polar lipids consisted mainly of phosphatidyldimethylethanolamine, phosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, sphingoglycolipid and some unidentified lipids. The major respiratory quinone was ubiquinone Q-10. Spermidine was the major polyamine observed. Phylogenetic analysis, DNA-DNA hybridization, chemotaxonomic and phenotypic analysis support the conclusion that strain LE124(T) represents a novel species within the genus Novosphingobium for which we propose the name Novosphingbium lindaniclasticum sp. nov. The type strain is LE124(T) (=CCM 7976(T)=DSM 25409(T)).

Comparing Pharmacological Potential of Freshwater Microalgae Carotenoids Towards Antioxidant and Anti-proliferative Activity on Liver Cancer (HUH7) Cell Line.

Chemical-based carotenoids have large implications to health as they may cause adverse side effects. Naturally occurring carotenoids mainly from microalgal sources are emerging as excellent substitute to combat cancer diseases. Astaxanthin is the most powerful antioxidant that derived from selected established microalgae with limited yield. Microalgal bioprospecting may provide the high-yielding sources for astaxanthin production. Hence, in the present research, freshwater microalgae Monoraphidium sp. (NCM no. 5585) and Scenedesmus obliquus (NCM no. 5586) were chosen to explore the unique potential of producing astaxanthin. Identification of bioactive metabolites in extracted carotenoid was analyzed through HPLC. Astaxanthin is identified as a major bioactive metabolite in both carotenoid fraction and ß carotene only in Scenedesmus obliquus. Antioxidant potential of microalgal carotenoids was obtained by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric-reducing antioxidant power (FRAP) assay. The anti-proliferation activity of the extracted carotenoid from Monoraphidium sp. and Scenedesmus obliquus was evaluated against hepatocellular liver carcinoma cell line HUH7 by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Higher astaxanthin in Monoraphidium sp. leads to boosted antioxidant and anti-proliferation activity contrary to Scenedesmus obliquus that possess both astaxanthin and ß carotene. Though freshwater microalgae have a huge potential to create beneficial metabolites like carotenoids, they are rarely studied in the pharmaceutical industry. This work was the first to investigate the anti-proliferative activity of Monoraphidium sp. and Scenedesmus obliquus carotenoid fraction on the HUH7 hepatocarcinoma cell line.

ISPD Catheter-related Infection Recommendations: 2023 Update.

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. The 2023 updated recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection. A new target for the overall exit site infection rate should be no more than 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations include clarified suggestion of exit site dressing cover and updated antibiotic treatment duration with emphasis on early clinical monitoring to ascertain duration of therapy. In addition to catheter removal and reinsertion, other catheter interventions including external cuff removal or shaving, and exit site relocation are suggested.

Genome sequence of Acinetobacter sp. strain HA, isolated from the gut of the polyphagous insect pest Helicoverpa armigera.

In this study, Acinetobacter sp. strain HA was isolated from the midgut of a fifth-instar larva of Helicoverpa armigera. Here, we report the draft genome sequence (3,125,085 bp) of this strain that consists of 102 contigs, 2,911 predicted coding sequences, and a G+C content of 41%.

Microbacterium amylolyticum sp. nov., isolated from soil from an industrial waste site.

A Gram-staining-positive, heterotrophic, aerobic, non-motile, non-endospore-forming, yellow-coloured rod, designated strain N5(T), was isolated from a soil sample collected at an industrial waste site in Noida, on the outskirts of Delhi, India. In phylogenetic analyses based on 16S rRNA gene sequences, strain N5(T) was most closely related to members of established species in the genus Microbacterium (with sequence similarities of approximately 94.0-97.6 %), particularly Microbacterium indicum LMG 23459(T) (97.59 %) and Microbacterium gubbeenense LMG 19263(T) (97.18 %). In DNA-DNA hybridization studies, however, none of the DNA-DNA relatedness values between strain N5(T) and members of the genus Microbacterium exceeded 11.3 %. The genomic DNA G+C content of the novel strain was 68 mol%. The chemotaxonomic characteristics of strain N5(T), which had MK-11 and MK-10 as its major menaquinones and anteiso-C(15 : 0) (45 %), anteiso-C(17 : 0) (37 %), iso-C(16 : 0) (8.5 %) and C(16 : 0) (4.5 %) as its predominant fatty acids, were consistent with classification in the genus Microbacterium. Peptidoglycan in the novel strain, which contained ornithine, alanine, glycine, homoserine, glutamic acid, 3-hydroxyglutamic acid, muramic acid and traces of N-glycolyl residues, was of type B2ß. The polar lipid profile of strain N5(T) comprised diphosphatidylglycerol, phosphatidylglycerol and an unknown glycolipid. The novel strain's major cell-wall sugars were glucose and galactose. Based on the phylogenetic, DNA-DNA hybridization, chemotaxonomic and phenotypic data, strain N5(T) represents a novel species within the genus Microbacterium for which the name Microbacterium amylolyticum sp. nov. is proposed; the type strain is N5(T) (= DSM 24221(T) = CCM 7881(T)).

Bioaccumulation and glutathione-mediated detoxification of copper and cadmium in Sphagnum squarrosum Crome Samml.

Physiological and biochemical responses, metal bioaccumulation and tolerance potential of Sphagnum squarrosum Crome Samml. to Cu and Cd were studied to determine its bioindication and bioremediation potential. Results suggest that glutathione treatment increases the metal accumulation potential and plays a definite role in heavy metal scavenging. High abundance of Sphagnum in metal-rich sites strongly suggests its high metal tolerance capabilities. This experiment demonstrates that S. squarrosum is able to accumulate and tolerate a high amount of metals and feasibility of its application as bioindicator and remediator test species of metal-contaminated environment.

Whole genome sequence of the rifamycin B-producing strain Amycolatopsis mediterranei S699.

Amycolatopsis mediterranei S699 is an actinomycete that produces an important antibiotic, rifamycin B. Semisynthetic derivatives of rifamycin B are used for the treatment of tuberculosis, leprosy, and AIDS-related mycobacterial infections. Here, we report the complete genome sequence (10.2 Mb) of A. mediterranei S699, with 9,575 predicted coding sequences.

Systematic barriers to the effective delivery of home dialysis in the United States: a report from the Public Policy/Advocacy Committee of the North American Chapter of the International Society for Peritoneal Dialysis.

Home dialysis, currently underused in the United States compared with other industrialized countries, likely will benefit from the newly implemented US prospective payment system. Not only is home dialysis less expensive from the standpoint of pure dialysis costs, but overall health system costs may be decreased by more subtle benefits, such as reduced transportation. However, many systematic barriers exist to the successful delivery of home dialysis. We organized these barriers into the categories of educational barriers (patient and providers), governmental/regulatory barriers (state and federal), and barriers specifically related to the philosophies and business practices of dialysis providers (eg, staffing, pharmacies, supplies, space, continuous quality improvement practices, and independence). All stakeholders share the goal of delivering home dialysis therapies in the most cost- and clinically effective and least problematic manner. Identification and recognition of such barriers is the first step. In addition, we have suggested action plans to stimulate the kidney community to find even better solutions so that collectively we may overcome these barriers.