Antimicrobial resistance landscape in a metropolitan city context using open drain wastewater-based metagenomic analysis.

One Health concept recognizes the inextricable interactions of diverse ecosystems and their subsequent effect on human, animal and plant health. Antimicrobial resistance (AMR) is a major One Health concern and is predicted to cause catastrophes if appropriate measures are not implemented. To understand the AMR landscape in a south Indian metropolitan city, metagenomic analysis of open drains was performed. The data suggests that in January 2022, macrolide class of antibiotics contributed the highest resistance of 40.1% in the city, followed by aminoglycoside- 24.4%, tetracycline- 11.3% and lincosamide- 6.7%. The 'mutations in the 23S rRNA gene conferring resistance to macrolide antibiotics' were the major contributor of resistance with a prevalence of 39.7%, followed by '16s rRNA with mutation conferring resistance to aminoglycoside antibiotics'- 22.2%, '16S rRNA with mutation conferring resistance to tetracycline derivatives'- 9.2%, and '23S rRNA with mutation conferring resistance to lincosamide antibiotics'- 6.7%. The most prevalent antimicrobial resistance gene (ARG) 'mutations in the 23S rRNA gene conferring resistance to macrolide antibiotics' was present in multiple pathogens including Escherichia coli, Campylobacter jejuni, Acinetobacter baumannii, Streptococcus pneumoniae, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Klebsiella pneumoniae and Helicobacter pylori. Most of the geographical locations in the city showed a similar landscape for AMR. Considering human mobility and anthropogenic activities, such an AMR landscape could be common across other regions too. The data indicates that pathogens are evolving and acquiring antibiotic resistance genes to evade antibiotics of multiple major drug classes in diverse hosts. The outcomes of the study are relevant not only in understanding the resistance landscape at a broader level but are also important for identifying the resistant drug classes, the mechanisms of gaining resistance and for developing new drugs that target specific pathways. This kind of surveillance protocol can be extended to regions in other developing countries to assess and combat the problem of antimicrobial resistance.

Caffeic Acid-Conjugated Budesonide-Loaded Nanomicelle Attenuates Inflammation in Experimental Colitis.

Ulcerative colitis is a multifactorial disease of the gastrointestinal tract which is caused due to chronic inflammation in the colon; it usually starts from the lower end of the colon and may spread to other portions of the large intestine, if left unmanaged. Budesonide (BUD) is a synthetically available second-generation corticosteroidal drug with potent local anti-inflammatory activity. The pharmacokinetic properties, such as extensive first-pass metabolism and quite limited bioavailability, reduce its therapeutic efficacy. To overcome the limitations, nanosized micelles were developed in this study by conjugating stearic acid with caffeic acid to make an amphiphilic compound. The aim of the present study was to evaluate the pharmacological potential of BUD-loaded micelles in a mouse model of dextran sulfate sodium-induced colitis. Micelles were formulated by the solvent evaporation method, and their physicochemical characterizations show their spherical shape under microscopic techniques like atomic force microscopy, transmission electron microscopy, and scanning electron microscopy. The in vitro release experiment shows sustained release behavior in physiological media. These micelles show cytocompatible behavior against hTERT-BJ cells up to 500 µg/mL dose, evidenced by more than 85% viable cells. BUD-loaded micelles successfully normalized the disease activity index and physical observation of colon length. The treatment with BUD-loaded micelles alleviates the colitis severity as analyzed in histopathology and efficiently, overcoming the disease severity via downregulation of various related cytokines (MPO, NO, and TNF-α) and inflammatory enzymes such as COX-2 and iNOS. Results of the study suggest that BUD-loaded nano-sized micelles effectively attenuate the disease conditions in colitis.

Structural and developmental dynamics of Matrix associated regions in Drosophila melanogaster genome.

BACKGROUND: Eukaryotic genome is compartmentalized into structural and functional domains. One of the concepts of higher order organization of chromatin posits that the DNA is organized in constrained loops that behave as independent functional domains. Nuclear Matrix (NuMat), a ribo-proteinaceous nucleoskeleton, provides the structural basis for this organization. DNA sequences located at base of the loops are known as the Matrix Attachment Regions (MARs). NuMat relates to multiple nuclear processes and is partly cell type specific in composition. It is a biochemically defined structure and several protocols have been used to isolate the NuMat where some of the steps have been critically evaluated. These sequences play an important role in genomic organization it is imperative to know their dynamics during development and differentiation. RESULTS: Here we look into the dynamics of MARs when the preparation process is varied and during embryonic development of D. melanogaster. A subset of MARs termed as "Core-MARs" present abundantly in pericentromeric heterochromatin, are constant unalterable anchor points as they associate with NuMat through embryonic development and are independent of the isolation procedure. Euchromatic MARs are dynamic and reflect the transcriptomic profile of the cell. New MARs are generated by nuclear stabilization, and during development, mostly at paused RNA polymerase II promoters. Paused Pol II MARs depend on RNA transcripts for NuMat association. CONCLUSIONS: Our data reveals the role of MARs in functionally dynamic nucleus and contributes to the current understanding of nuclear architecture in genomic context.

Nanotechnology-Assisted, Single-Chromophore-Based White-Light-Emitting Organic Materials with Bioimaging Properties.

White-light-emitting (WLE) organic materials, especially small molecules comprising a single chromophoric unit, have received much attention due to their tremendous use in modern-day electronic devices and biomaterials. They can increase the efficiency and lifetime of devices compared to the currently used combination approach. Herein, we explored a small symmetric push-pull organic molecule Hexyl-TCBD with a single 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) chromophoric unit containing urea as a key functional group on an acceptor-donor∼donor-acceptor (A-D∼D-A) backbone for its ability to show white-light emission in solution as well as in the solid state. The luminescence was absent in the solid state due to the H-bonding- and π-stacking-driven quenching processes, while emission behavior in solution was tunable with variable CIE chromaticity index values via hydrogen (H)-bonding-governed disaggregation phenomena. Translation of WLE from the Hexyl-TCBD solution to a solid state was demonstrated by utilizing nonemissive polystyrene (80 wt % with respect to the chromophore) as the matrix to obtain WLE nanofibers (made by the electrospun technique) via segregating the molecules. The optical microscopy study validated the WLE nanofibers. The presence of multicolor photoluminescence, including white light, could be fine-tuned through various excitation wavelengths, solvent polarities, and polystyrene matrices. Furthermore, the detailed photophysical studies, including lifetime measurements, indicated that the inherent intramolecular charge transfer (ICT) bands of Hexyl-TCBD exhibit better ICT state stabilization by space charge distribution through the modulation of H-bonding between urea groups. Finally, a cytotoxicity study was performed for Hexyl-TCBD on normal and cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to explore bioimaging applications in biosystems. MTT results revealed significant toxicity toward cancer cells, whereas normal cells exhibited good biocompatibility.

Synthetic Tunability and Biophysical Basis for Fabricating Highly Fluorescent and Stable DNA Copper Nanoclusters.

The real motivation in the present work is to tune the synthesis variables that can result in a highly fluorescent and stable DNA copper nanocluster (CuNC) and also to understand the intricate mechanism behind this process. Here, carefully optimized concentrations of various reactants enabled the creation of a DNA-encapsulated CuNC for AT-DNA, displaying a size of <1.0 nm as confirmed by transmission electron microscopy and dynamic light scattering. The extremely small size of the AT-DNACuNC supports the discrete electronic transitions, also characterized by an exceptionally strong negative circular dichroism (CD) band around 350 nm, whose intensity is well correlated with the observed strong fluorescence emission intensity. This remarkably strong CD can open new applications in the detection and quantification of a specific DNACuNC. Further, time-dependent fluorescence analysis suggested stronger photostabilization of these DNACuNCs. The simulation study, based on Cu ion distribution, explained how AT-DNA is a better candidate for NC formation than GC-DNA. In conclusion, the better-tuned synthesis procedure has resulted in a highly compact, well-defined three-dimensional conformation that promotes a more favorable microenvironment to sequester a DNA-based CuNC with high brightness and outstanding photostability.

Release of Mediator Enzyme ß-Hexosaminidase and Modulated Gene Expression Accompany Hemocyte Degranulation in Response to Parasitism in the Silkworm Bombyx mori.

In insects infections trigger hemocyte-mediated immune reactions including degranulation by exocytosis; however, involvement of mediator enzymes in degranulation process is unknown in insects. We report here that in silkworm Bombyx mori, infection by endoparasitoid Exorista bombycis and microsporidian Nosema bombycis activated granulation in granulocytes and promoted degranulation of accumulated structured granules. During degranulation the mediator lysosomal enzyme ß-hexosaminidase showed increased activity and expression of ß-hexosaminidase gene was enhanced. The events were confirmed in vitro after incubation of uninfected hemocytes with E. bombycis larval tissue protein. On infection, cytotoxicity marker enzyme lactate dehydrogenase (LDH) was released from the hemocytes illustrating cell toxicity. Strong positive correlation (R2 = 0.71) between LDH activity and ß-hexosaminidase released after the infection showed parasitic-protein-induced hemocyte damage and accompanied release of the enzymes. Expression of ß-hexosaminidase gene was enhanced in early stages after infection followed by down regulation. The expression showed positive correlation (R2 = 0.705) with hexosaminidase activity pattern. B. mori hexosaminidase showed 98% amino acid similarity with that of B. mandarina showing origin from same ancestral gene; however, 45-60% varied from other lepidopterans showing diversity. The observation signifies the less known association of hexosaminidase in degranulation of hemocytes induced by parasitic infection in B. mori and its divergence in different species.

Targeting genes involved in nucleopolyhedrovirus DNA multiplication through RNA interference technology to induce resistance against the virus in silkworms.

RNA interference (RNAi) has become an efficient tool for inducing resistance to viruses in many organisms. In this study, Escherichia coli cells were engineered to produce stable double-stranded RNA (dsRNA) against the nucleopolyhedrosis virus to elicit RNAi in silkworms. The immediate-early-1 (ie-1) and late expression factor-1 (lef-1) genes of the Bombyx mori nucleopolyhedrovirus (BmNPV) involved in viral DNA multiplication were cloned in the plasmid L4440 under the influence of the double T7 promoter and transformed to E. coli HT115 DE3 host cells. On induction with isopropyl ß-D-thiogalactopyranoside, these cells efficiently produced dsRNA of the cloned genes. The B. mori larvae were fed with 50 µL of E. coli cells expressing ie-1 and lef-1 dsRNAs (each approximately 25 µg) to elicit RNAi. The semi-quantitative and quantitative PCR analysis of RNA from the midgut of the dsRNA-fed larvae revealed a significant reduction in the expression of the target genes involved in BmNPV multiplication, which restricted virus copy numbers to 100 compared with 1.9 × 105 in the infected controls. Furthermore, the dsRNA-fed infected larvae showed > 50% increased survivability compared with the infected controls. The study revealed the successful use of bacteria as vectors for efficiently delivering dsRNA to elicit RNAi against BmNPV in silkworms.

Recombinant expression of sericin-cecropin fusion protein and its functional activity.

OBJECTIVE: Silk sericin is a natural polymer with potential utility in biomedical and biotechnological applications. Recombinantly expressed sericin ensures a source of pure protein with no contamination and with multiple properties when expressed as a fusion protein. Hence, the present paper aims to recombinantly express a functional silk sericin fusion protein. RESULTS: In order to develop a more effective sericin protein, we have attempted to recombinantly express a part of sericin sequence, which represents a highly conserved and internally repetitive unit of the sericin1 protein, and its fusion with cecropin B, a potent antimicrobial peptide. Both difficult-to-express proteins were expressed in Escherichia coli and purified by nickel-charged affinity resin. Further, functional assay demonstrated that both proteins were individually active against Gram-positive and negative bacteria, with enhanced bactericidal activity observed in sericin-cecropin B fusion protein. CONCLUSIONS: To our knowledge, this is the first report not only on the recombinant expression of sericin as a fusion protein but also the bactericidal possibility of the 38-amino acid serine-rich motif of sericin protein. We also discuss the potential biomedical and biotechnological applications of this sericin hybrid protein.

PERF: an exhaustive algorithm for ultra-fast and efficient identification of microsatellites from large DNA sequences.

Motivation: Microsatellites or Simple Sequence Repeats (SSRs) are short tandem repeats of DNA motifs present in all genomes. They have long been used for a variety of purposes in the areas of population genetics, genotyping, marker-assisted selection and forensics. Numerous studies have highlighted their functional roles in genome organization and gene regulation. Though several tools are currently available to identify SSRs from genomic sequences, they have significant limitations. Results: We present a novel algorithm called PERF for extremely fast and comprehensive identification of microsatellites from DNA sequences of any size. PERF is several fold faster than existing algorithms and uses up to 5-fold lesser memory. It provides a clean and flexible command-line interface to change the default settings, and produces output in an easily-parseable tab-separated format. In addition, PERF generates an interactive and stand-alone HTML report with charts and tables for easy downstream analysis. Availability and implementation: PERF is implemented in the Python programming language. It is freely available on PyPI under the package name perf_ssr, and can be installed directly using pip or easy_install. The documentation of PERF is available at https://github.com/rkmlab/perf. The source code of PERF is deposited in GitHub at https://github.com/rkmlab/perf under an MIT license. Contact: tej@ccmb.res.in. Supplementary information: Supplementary data are available at Bioinformatics online.

Selection of suitable reference genes for quantitative real-time PCR gene expression analysis in Mulberry (Morus alba L.) under different abiotic stresses.

Mulberry (Morus alba L.) is the sole food source for the mulberry silkworm, Bombyx mori and therefore important for sericulture industry. Different abiotic stress conditions like drought, salt, heat and cold stress adversely affect the productivity and quality of mulberry leaves. Quantitative real time PCR (qPCR) is a reliable and widely used method to identify abiotic stress responsive genes and molecular mechanism in different plant species. Selection of suitable reference genes is important requirement for normalizing the expression of genes through qRT-PCR study. In the present study, we have selected eight candidate reference genes in mulberry for analyzing their expression stability in different abiotic stress treatments including drought, salt, heat and cold stresses. The expression stability of these reference genes was determined using geNorm, NormFinder and RefFinder statistical algorithms. The results showed that Ubiquitin and protein phosphatase 2A regulatory subunit A (PP2A) were the most stable genes across all the treatment samples. However, analysis of individual stresses revealed different expression profiles and stability of reference genes. Actin3 and PP2A were most stable in drought and salt conditions respectively. RPL3 most preferred in heat stress and Ubiquitin was most stable in cold stress. We propose the ubiquitin and PP2A are the preferred reference genes for normalization of gene expression data from abiotic stresses. In addition, Actin3 are preferred for drought stress, PP2A for salt stress, RPL3 for heat stress and Ubiquitin for cold stress studies.

Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects.

Cancer remains the topmost disorders of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.

Role of abd-A and Abd-B in development of abdominal epithelia breaks posterior prevalence rule.

Hox genes that determine anteroposterior body axis formation in all bilaterians are often found to have partially overlapping expression pattern. Since posterior genes dominate over anterior Hox genes in the region of co-expression, the anterior Hox genes are thought to have no function in such regions. In this study we show that two Hox genes have distinct and essential functions in the same cell. In Drosophila, the three Hox genes of the bithorax complex, Ubx, abd-A and Abd-B, show coexpression during embryonic development. Here, we show that in early pupal abdominal epithelia, Ubx does not coexpress with abd-A and Abd-B, while abd-A and Abd-B continue to coexpress in the same nuclei. The abd-A and Abd-B are expressed in both histoblast nest cells and larval epithelial cells of early pupal abdominal epithelia. Further functional studies demonstrate that abd-A is required in histoblast nest cells for their proliferation and suppression of Ubx to prevent first abdominal segment like features in posterior segments while in larval epithelial cells it is required for their elimination. We also observed that these functions of abd-A are required in its exclusive as well as the coexpression domain with that of Abd-B. The expression of Abd-B is required in histoblast nest cells for their identity while it is dispensable in the larval epithelial cells. The higher level of Abd-B in the seventh abdominal segment, that down-regulates abd-A expression, leads this segment to be absent in males or of smaller size in females. We also show that abd-A in histoblast nest cells positively regulates expression of wingless for the formation of the abdominal epithelia. Our study reveals an exception to the rule of posterior prevalence and shows that two different Hox genes have distinct functions in the same cell, which is essential for the development of abdominal epithelia.

Subclinical respiratory dysfunction in chronic cervical cord compression: a pulmonary function test correlation.

OBJECTIVE Respiratory abnormalities are well documented in acute spinal cord injury; however, the literature available for respiratory dysfunction in chronic compressive myelopathy (CCM) is limited. Respiratory dysfunction in CCM is often subtle and subclinical. The authors studied the pattern of respiratory dysfunction in patients with chronic cord compression by using spirometry, and the clinical and surgical implications of this dysfunction. In this study they also attempted to address the postoperative respiratory function in these patients. METHODS A prospective study was done in 30 patients in whom cervical CCM due to either cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) was diagnosed. Thirty age-matched healthy volunteers were recruited as controls. None of the patients included in the study had any symptoms or signs of respiratory dysfunction. After clinical and radiological diagnosis, all patients underwent pulmonary function tests (PFTs) performed using a standardized Spirometry Kit Micro before and after surgery. The data were analyzed using Statistical Software SPSS version 13.0. Comparison between the 2 groups was done using the Student t-test. The Pearson correlation coefficient was used for PFT results and Nurick classification scores. A p value < 0.05 was considered significant. RESULTS Cervical spondylotic myelopathy (prolapsed intervertebral disc) was the predominant cause of compression (n = 21, 70%) followed by OPLL (n = 9, 30%). The average patient age was 45.06 years. Degenerative cervical spine disease has a relatively younger onset in the Indian population. The majority of the patients (n = 28, 93.3%) had compression at or above the C-5 level. Ten patients (33.3%) underwent an anterior approach and discectomy, 11 patients (36.7%) underwent decompressive laminectomy, and the remaining 9 underwent either corpectomy with fusion or laminoplasty. The mean preoperative forced vital capacity (FVC) (65%) of the patients was significantly lower than that of the controls (88%) (p < 0.001). The mean postoperative FVC (73.7%) in the patients showed significant improvement compared with the preoperative values (p = 0.003). The mean postoperative FVC was still significantly lower than the control value (p = 0.002). The mean preoperative forced expiratory volume in 1 second (FEV1) (72%) of the patients was significantly lower than that of the controls (96%) (p < 0.001). The mean postoperative FEV1 (75.3%) in the cases showed no significant improvement compared with the preoperative values (p = 0.212). The mean postoperative FEV1 was still significantly lower than the control value (p < 0.001). The mean postoperative FEV1/FVC was not significantly different from the control value (p = 0.204). The mean postoperative peak expiratory flow rate was significantly lower than the control value (p = 0.01). The mean postoperative maximal voluntary ventilation was still significantly lower than the control value (p < 0.001). On correlating the FVC and Nurick scores using the Pearson correlation coefficient, a negative correlation was found. CONCLUSIONS There is subclinical respiratory dysfunction and significant impairment of various lung capacities in patients with CCM. The FVC showed significant improvement postoperatively. Respiratory function needs to be evaluated and monitored to avoid potential respiratory complications.

2-AZETIDINONE DERIVATIVES: SYNTHESIS, ANTIMICROBIAL, ANTICANCER EVALUATION AND QSAR STUDIES.

A series of 2-azetidinone derivatives was synthesized from hippuric acid and evaluated for its in vitro antimicrobial and anticancer activities. Antimicrobial properties of the title compounds were investigated against Gram positive and Gram negative bacterial as well as fungal strains. Anticancer activity was performed against breast cancer (MCF7) cell lines. Antimicrobial activity results revealed that N-{2-[3-chloro-2-(2- chlorophenyl)-4-oxoazetidin-1-ylamino]-2-oxoethyl}benzamide (4) was found to be the most potent antimicrobial agent. Results of anticancer study indicated that the synthesized compounds exhibited average anticancer potential and N-[2-(3-chloro-2-oxo-4-styrylazetidin-1-ylamino)-2-oxoethyl]benzamide (17) was found to be most potent anticancer agent against breast cancer (MCF7) cell lines. QSAR models indicated that the antibacterial, antifungal and the overall antimicrobial activities of the synthesized compounds were governed by topological parameters, Balaban index (J) and valence zero and first order molecular connectivity indices (°χv and ¹χv).

SYNTHESIS, ANTIMICROBIAL, ANTICANCER EVALUATION AND QSAR STUDIES OF THIAZOLIDIN-4-ONE DERIVATIVES.

In this study, a novel series of 4-thiazolidinone derivatives (1-17) was synthesized and evaluated for its in vitro antimicrobial and anticancer potentials. N-(2-(5-(4-nitrobenzylidene)-2-(4-chlorophenyl)-4-oxothia- zolidin-3-ylamino)-2-oxoethyl) benzamide (7, pMICam = 1.86 µM/mL) was found to be the most active antimi- crobial agent. The anticancer study results demonstrated that N-(2-(5-(4-hydroxybenzylidene)-2-(4- methoxyphenyl)-4-oxothiazolidin-3-ylamino)-2-oxoethyl) benzamide (10, IC50 = 18.59 µM) was the most active anticancer agent. QSAR studies indicated the importance of topological parameter, Kier's α third order shape index (κα3) as well as electronic parameters, cosmic total energy (cos E) and energy of highest occupied molecular orbital (HOMO) in describing the antimicrobial activity of synthesized compounds.

Rupture of DNA aptamer: New insights from simulations.

Base-pockets (non-complementary base-pairs) in a double-stranded DNA play a crucial role in biological processes. Because of thermal fluctuations, it can lower the stability of DNA, whereas, in case of DNA aptamer, small molecules, e.g., adenosinemonophosphate and adenosinetriphosphate, form additional hydrogen bonds with base-pockets termed as "binding-pockets," which enhance the stability. Using the Langevin dynamics simulations of coarse grained model of DNA followed by atomistic simulations, we investigated the influence of base-pocket and binding-pocket on the stability of DNA aptamer. Striking differences have been reported here for the separation induced by temperature and force, which require further investigation by single molecule experiments.

Disappearance of "Elongated Pony Tail Sign" Following Chemoradiotherapy in a Case of Primary Cerebellopontine Angle Ependymoma With Spinal Drop Metastasis: 18 F-FDG PET/CT Scan Findings.

ABSTRACT: Ependymomas are rare glial tumors that commonly arise from the lining cells of ventricular system and constitute ~10% of intracranial pediatric malignancies. The incidence of ependymoma in adults is rare. Due to close approximation with the ventricular system, subtentorial ependymomas are more prone to show cerebrospinal fluid metastasis compared with supratentorial ependymomas. We present a case of subtentorial cerebellopontine angle ependymoma with diffuse spinal drop metastases showing "elongated pony tail appearance" in a 69-year-old man with complete metabolic response on 18 F-FDG PET/CT imaging following chemoradiotherapy.

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances-which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes.

Systematic review and meta-analysis of studies comparing baseline D-dimer level in stroke patients with or without cancer: Strength of current evidence.

Objectives: D-dimer levels are increased in stroke and cancer. Cancer patients are at a higher risk of stroke. However, the evidence is unclear if high D-dimer in stroke patients can suggest the diagnosis of concomitant cancer or the development of stroke in a cancer patient. The objective is to assess the evidence available on the baseline D-dimer level in stroke patients with and without cancer. Materials and Methods: We conducted the systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched PUBMED, Cochrane, ScienceDirect, and Scopus for potentially eligible articles published till June 2023. All the review steps were iterative and done independently by two reviewers. The Newcastle-Ottawa scale tool was used to assess the quality of included studies for case control and cohort studies and the Agency for Healthcare Research and Quality tool for cross-sectional studies. The qualitative synthesis is presented narratively, and quantitative synthesis is shown in the forest plot using the random effects model. I2 of more than 60% was considered as high heterogeneity. Results: The searches from all the databases yielded 495 articles. After the study selection process, six papers were found eligible for inclusion in the qualitative and quantitative synthesis. In the present systematic review, 2651 patients with ischemic infarcts are included of which 404 (13.97%) patients had active cancer while 2247 (86.02%) did not. The studies included were of high quality and low risk of bias. There were significantly higher baseline D-dimer levels in stroke patients with cancer than in non-cancer patients with a mean difference of 4.84 (3.07-6.60) P < 0.00001. Conclusion: D-dimer is a simple and relatively non-expensive biomarker that is increased to significant levels in stroke patients, who have cancer and therefore may be a tool to predict through screening for active or occult cancer in stroke patients.

Scaling of hysteresis loop of interacting polymers under a periodic force.

Using Langevin dynamics simulations, we study a simple model of interacting-polymer under a periodic force. The extension curves strongly depend on the magnitude of the amplitude (F) and the frequency (ν) of the applied force. In low frequency limit, the system retraces the thermodynamic path. At higher frequencies, response time is greater than the external time scale for change of force, which restrict the biomolecule to explore a smaller region of phase space that results in hysteresis of different shapes and sizes. We show the existence of dynamical transition, where area of hysteresis loop approaches to a large value from nearly zero value with decreasing frequency. The area of hysteresis loop is found to scale as F(α)ν(ß) for the fixed length. These exponents are found to be the same as of the mean field values for a time dependent hysteretic response to periodic force in case of the isotropic spin.