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Abstract Macrophages assume diverse phenotypes and functions in response to cues from the microenvironment. Earlier we reported an anti-inflammatory effect of Collagenase Santyl® Ointment (CSO) and the active constituent of CSO (CS-API) on wound macrophages in resolving wound inflammation indicating roles beyond debridement in wound healing. Building upon our prior finding, this study aimed to understand the phenotypes and subsets of macrophages following treatment with CS-API. scRNA-sequencing was performed on human blood monocyte-derived macrophages (MDM) following treatment with CS-API for 24 h. Unbiased data analysis resulted in the identification of discrete macrophage subsets based on their gene expression profiles. Following CS-API treatment, clusters 3 and 4 displayed enrichment of macrophages with high expression of genes supporting extracellular matrix (ECM) function. IPA analysis identified the TGFβ-1 pathway as a key hub for the CS-API-mediated ECM-supportive phenotype of macrophages. Earlier we reported the physiological conversion of wound-site macrophages to fibroblasts in granulation tissue and impairment of such response in diabetic wounds, leading to compromised ECM and tensile strength. The findings that CSO can augment the physiological conversion of macrophages to fibroblast-like cells carry significant clinical implications. This existing clinical intervention, already employed for wound care, can be readily repurposed to improve the ECM response in chronic wounds.

Abstract Background Metastasis has been a cause of the poor prognosis and cancer relapse of triple‐negative breast cancer (TNBC) patients. The metastatic nature of TNBC is contributed by the breast cancer stem cells (CSCs) which have been implicated in tumorigenesis. Higher expression of epidermal growth factor receptor (EGFR) in breast CSCs has been used as a molecular target for breast cancer therapeutics. Thus, it necessitates the design and generation of efficacious EGFR inhibitors to target the downstream signaling associated with the cellular proliferation and tumorigenesis of breast cancer. Aim To generate efficacious EGFR inhibitors that can potentiate the chemotherapeutic‐mediated mitigation of breast cancer tumorigenesis. Methods and Results We identified small molecule EGFR inhibitors using molecular docking studies. In‐vitro screening of the compounds was undertaken to identify the cytotoxicity profile of the small‐molecule EGFR inhibitors followed by evaluation of the non‐cytotoxic compounds in modulating the doxorubicin‐induced migration, in‐vitro tumorigenesis potential, and their effect on the pro‐apoptotic genes' and protein markers' expression in TNBC cells. Compound 1e potentiated the doxorubicin‐mediated inhibitory effect on proliferation, migration, in‐vitro tumorigenesis capacity, and induction of apoptosis in MDA‐MB‐231 cells, and in the sorted CD24+‐breast cancer cells and CD24−/CD44+‐breast CSC populations. Orthotopic xenotransplantation of the breast CSCs‐induced tumors in C57BL/6J mice was significantly inhibited by the low dose of Doxorubicin in the presence of compound 1e as depicted by molecular and immunohistochemical analysis. Conclusion Thus, the study suggests that EGFR inhibition‐mediated sensitization of the aggressive and metastatic breast CSCs in TNBCs toward chemotherapeutics may reduce the relapse of the disease.

A strain of Penicillium citrinum isolate-ABRF3 collected from the Achanakmar Biosphere, India, was examined for its bioactive potential. Under optimized conditions, secondary metabolites were extracted from the fungus using the solvent extraction method, and all fractions were assessed for antioxidant, antimicrobial, anti-aging, and antiproliferative activity. The highest antioxidant activity was shown by Penicillium citrinum ethanolic extract, i.e., 80%, 79%, 77%, and 75% when assessed by 2,2-diphenyl 1-picrylhydrazyl, Ferric reducing power, Phosphomolybdenum, and 2, 2’-azino-bis3-ethylbenzthiazoline-6-sulfonic assays, respectively. A maximum inhibition zone of 17.18 ± 1.3 mm was observed against pathogenic bacteria Staphylococcus aureus in the ethyl acetate column fraction compared with standard antibiotics. Ethyl acetate column fraction demonstrated meaningful anti-aging activity against Yeast mutant strain, BY4742, along with methanol and chloroform column fraction depicted a substantial DNA fragmentation and antiproliferative action against a set of mammalian cancer cell lines. The Gas Chromatography with Mass Spectroscopy and Nuclear Magnetic Resonance analysis identified (E)-9-Octadecenoic acid ethyl ester as a significant secondary metabolite in the extract. In silico molecular docking was performed for identified metabolite (E)-9-Octadecenoic acid ethyl ester to ascertain its putative role in extract bioactivity, with various anti-aging and anticancer targets.

A novel nano-formulation (NF) that sensitizes Acinetobacter baumannii (AB) to otherwise ineffective colistin is described in the present study. Infections due to multidrug resistant (MDR) AB represent a major therapeutic challenge, especially in situations of pre-existing colistin resistance (colR). Subsequently, boosting the effectiveness of colistin would be a better alternative tactic to treat AB infections rather than discovering a new class of antibiotics. We have previously demonstrated an NF comprising self-assembled guanidinium and ionic silver nanoparticles [AD-L@Ag(0)] to have anti-biofilm and bactericidal activity. We report NF AD-L@Ag(0) for the very first time for the potentiation of colistin in Gram-negative colistin-resistant bacteria. Our results implied that a combination of clinically relevant concentrations of colistin and AD-L@Ag(0) significantly decreased colistin-resistant AB bacterial growth and viability, which otherwise was elevated in the presence of only colistin. In this study, we have described various combinations of minimum inhibitory concentration (MIC) of colistin (MICcol, 1/2 MICcol, and 1/4 MICcol) and that of AD-L@Ag(0) [MICAD-L@Ag(0), 1/2 MICAD-L@Ag(0), and 1/4 MICAD-L@Ag(0)] and tested them against MDR AB culture. The results (in broth as well as in solid media) signified that AD-L@Ag(0) was able to potentiate the anti-microbial activity of colistin at sub-MIC concentrations. Furthermore, the viability and metabolic activity of bacterial cells were also measured by CTC fluorescence assay and ATP bioluminescence assay. The results of these assays were in perfect concordance with the scores of cultures (colony forming unit and culture turbidity). In addition, quantitative real-time PCR (qRT-PCR) was performed to unveil the expression of selected genes, DNAgyrA, DNAgyrB, and dac. These genes introduce negative supercoiling in the DNA, and hence are important for basic cellular processes. These genes, due to mutation, modified the Lipid A of bacteria, further resisting the uptake of colistin. Therefore, the expression of these genes was upregulated when AB was treated with only colistin, substantiating that AB is resistant to colistin, whereas the combinations of MICcol + MICAD-L@Ag(0) downregulated the expression of these genes, implying that the developed formulation can potentiate the efficiency of colistin. In conclusion, AD-L@Ag(0) can potentiate the proficiency of colistin, further enhancing colistin-mediated death of AB by putatively disrupting the outer membrane (OM) and facilitating bacterial death.

Abstract Chronic wounds show necroptosis from which keratinocytes must be protected to enable appropriate wound re-epithelialization and closure. Poloxamers, a class of synthetic triblock copolymers, are known to be effective against plasma membrane damage (PMD). The purpose of this study is to evaluate the efficacy of a specific poloxamer, surfactant polymer dressing (SPD), which is currently used clinically as wound care dressing, against PMD in keratinocytes. Triton X-100 (TX100) at sub-lytic concentrations caused PMD as demonstrated by the efflux of calcein and by the influx of propidium iodide and FM1-43. TX100, an inducer of necroptosis, led to mitochondrial fragmentation, depletion of nuclear HMGB1, and activation of signaling complex associated with necroptosis (i.e., activation of RIP3 and phosphorylation of MLKL). All responses following exposure of human keratinocytes to TX100 were attenuated by pre- or co-treatment with SPD (100 mg/ml). The activation and translocation of phospho-MLKL to the plasma membrane, taken together with depletion of nuclear HMGB1, characterized the observed cell death as necroptosis. Thus, our findings show that TX100-induced plasma membrane damage and death by necroptosis were both attenuated by SPD, allowing keratinocyte survival. The significance of such protective effects of SPD on keratinocytes in wound re-epithelialization and closure warrant further studies.

This paper presents a comparative performance analysis of a single-stage GaAs Low-Noise Power Amplifier (LNPA) fabricated in a $0.25~\mu $ m pHEMT process to mitigate co-site interference across multiple frequencies in the L- and S-bands. We compare five different designs from 1.2 to 3.8 GHz, each offering a minimum bandwidth of 300 MHz. Designed bandwidth is sufficient to cover several popular 5G NR FR1 channels as well as suitable for carrier aggregation in the LTE bands. An Output 1-dB compression point (OP1dB) of 27.5 dBm, noise figure (NF) below 1 dB and an Output 3rd-order Intercept Point (OIP3) up to 40 dBm is achieved. Adjacent Channel Leakage Ratio (ACLR) measurements are performed at 2.5 GHz with a Peak to Average Power Ratio (PAPR) of 11.8 dB. We achieve an ACLR of −25 dBc at 25 dBm of output power for a 20 MHz, 16-QAM modulation signal, while the corresponding power added efficiency & Drain-efficiency (DE) are, on average, more than 47% & 50% respectively. An integrated Electro-Static-Discharge (ESD) limiter is also incorporated, which can tolerate up to 350 V Human Body Model (HBM) and 125 V Charged Device Model (CDM) without failure. The design occupies a footprint of only 0.325 mm2.

Summary: Thin film membranes of covalent organic frameworks are promising for high-permeance molecular separation. However, their synthesis needs a high temperature or longer reaction time, unsuitable for large-scale fabrication of thin film composite membranes. The ultrathin film of porous organic polymers as a separation layer of the composite membrane could be a close alternative to COF membranes. Here we report transition metal ion-catalyzed room temperature fabrication of the ultrathin (≈12 nm) polyimine nanofilms via interfacial polymerization of melamine and triformylphloroglucinol onto hydrolyzed polyacrylonitrile support within a short reaction time. Composite membranes exhibit high water permeance (≈78 L m−2 h−1 bar−1), high rejection (99.6%) of brilliant blue R (825.9 g mol−1), low rejection of NaCl (≈1.8%) and Na2SO4 (≈17%), and enable efficient molecular separation. The role of metal ion catalysts for large-area fabrication of the ultrathin polyimine nanofilm membranes used for molecular separation is demonstrated.

Summary: The gastrointestinal (GI) tract is one of the major sites for reactive oxygen species generation (ROS). Physiological ROS, lower than the threshold concentration, is beneficial for human physiology to preserve gut functional integrity. However, ROS generated in large quantities in presence of external stimuli overwhelms the cellular antioxidant defense mechanism and results in oxidative damage and associated physiological disorder. Graphene quantum dots (GQDs) are a class of carbon-based nanomaterials that have attracted tremendous attention not only for their tunable optical properties but also for their broad-spectrum antioxidant properties. In this report we have shown that GQDs are highly efficient in scavenging ROS and suppressing stress-induced gastric ulcers by targeting the MMP-9 pathway and reducing the inflammatory burden by suppressing excessive oxidative stress by inducing high caspase activity, overproduction of Bax, and downregulation of BCL2.

Abstract The present study evaluated the potential biological activities of rhizospheric fungi isolated from the Achanakmar Biosphere Reserve, India. Fungus, Talaromyces purpureogenus isolate-ABRF2 from the soil of the Achanakmar biosphere was characterized by using morphological, biochemical and molecular techniques. Fungus was screened for the production of secondary metabolites using a specific medium. The metabolites were extracted using a suitable solvent and each fraction was subsequently evaluated for their antioxidant, antimicrobial, antiproliferative and anti-aging properties. The ethanolic extract depicted the highest antioxidant activity with 83%, 79%, 80% and 74% as assessed by ferric reducing power, 2,2-diphenyl 1-picrylhydrazyl, 2,2′-azino-bis3-ethylbenzthiazoline-6-sulfonic and phosphomolybdenum assays, respectively. Similarly, ethanolic extracts depicted marked antimicrobial activity as compared with standard antibiotics and antifungal agents as well as demonstrated significant antiproliferative property against a panel of mammalian cancer cell lines. Furthermore, different fractions of the purified ethanolic extract obtained using adsorption column chromatography were evaluated for antiproliferative property and identification of an active metabolite in the purified fraction using gas chromatography–mass spectroscopy and nuclear magnetic resonance techniques yielded 3-methyl-4-oxo-pentanoic acid. Thus, the present study suggests that the active metabolite 3-methyl-4-oxo-pentanoic acid extracted from Talaromyces purpureogenus isolate-ABRF2 has a potential antiproliferative, anti-aging, and antimicrobial therapeutic properties that will be further evaluated using in vivo studies in future.

Objective: The objective of this study is to compare the outcome of caesarean section post-op wound in patients after either approximation or after non-approximation of the subcutaneous fat layer. Methodology: 390 women who underwent emergency caesarean section having abdominal fat thickness of more than 2 cm were randomly allocated in two groups of 195 each. The subcutaneous fat layer was approximated in the patients of group A. The condition of wound in each patient was examined on 5th postoperative day and the complications, if any were categorised into wound disruption, seroma, hematoma or infection. Then further postoperative analgesic, antibiotic doses and hospital stay duration were compared among two group patients. Result: Among 195 patients of Group A, only 20 (10.26%) had wound complications whereas in Group B, 55 patients had wound complications (28.21 %). In group A patients, only 2.5 % needed secondary suturing whereas in group B patients, 18.9 % needed secondary suturing. Conclusion: Approximation of the subcutaneous tissues separately significantly reduces wound complications, requirement of secondary suturing along with a significant reduction in the duration of hospital stay.

Objective: To find out prevalence of congenital heart disease in pregnant women and its cardiac, obstetric and neonatal outcome. Methodology: A prospective study was conducted on 74 mothers who had congenital heart disease and admitted in Obstetrics and Gynaecology department during a period of December 2013 to December 2017. Baseline data were collected before pregnancy or at the first antenatal visit. These included clinical presentation, ECG, chest X ray, echodoppler study and subsequently maternal cardiac event, obstetric outcome, neonatal event and risk stratification of bad obstetric outcome. Result: During the study period 74 women having congenital heart disease (CHD) were seen. The prevalence of congenital heart disease was 0.14%. Most of the patients had atrial septal defect (ASD) (35%). Normal delivery was in 18 numbers of patients and most of these were ASD and pulmonary stenosis. Large number of patients had developed complication of sustained arrhythmia (41%). Pulmonary oedema was documented in 8 patients. Seven patients expired during labour and puerperium. Regarding fetal outcome 58% pregnancy had intrauterine growth restriction, 67% had preterm birth and 8% had neonatal death. Conclusion: Maternal and neonatal complication rates are considerably high in pregnant women with congenital heart disease.

At the site of injury, macrophages exit their characteristic phenotype undergoing direct conversion to fibroblasts. Keratinocyte-derived miR-21, packaged in extracellular vesicles, enables such plasticity which accounts for the vast majority of all fibroblasts in the granulation tissue.

Mouse bone marrow stromal stem/progenitor cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and Hematopoietic Stem and Progenitor Cells (HSPCs) with differential proliferative potentials were investigated for identifying epigenetic signals that can modulate their growth. In the present study, immunodepletion of granulo-monocytic (CD11b) and erythroid (Ter119) population yielded CD11b−/Ter119− cells, capable of differentiating into chondrogenic, osteogenic and adipogenic cells. Enrichment of the CD11b+ population by positive selection of multipotent stem/progenitor marker (CD133) yielded CD11b+/CD133+ cells, efficiently differentiated into hematopoietic lineages. Molecular characterization revealed the expression of BMSC and HSPC markers in CD11b−/Ter119− and CD11b+/CD133+ sorted populations, respectively. Cell expansion studies depicted a higher growth rate and percentage of proliferating cells in G2/M phase of cell cycle in BMSCs (13.9 ± 2.9%) as compared with HSPCs (5.8 ± 0.8%). Analysis of the HDACs gene expression revealed a differential expression pattern in BMSCs and HSPCs that modulates the cell cycle genes. Trichostatin A (TSA)-mediated HDAC inhibition led to an increased level of AcH3 and AcH4 along with cyclins B1 and D2. Chromatin immunoprecipitation revealed alleviation of HDAC2 and HDAC3 binding by TSA on cyclins B1 and D2 promoter, thereby enhancing cell proliferation. This study identifies epigenetic modulation on the proliferative potential of BMSCs and HSPCs for stem cell transplantation therapies.

Low bioavailability and/or survival at the injury site of transplanted stem cells necessitate its delivery using a biocompatible, biodegradable cell delivery vehicle. In this dataset, we report the application of a porous biocompatible, biodegradable polymer network that successfully delivers bone marrow stem cells (BMSCs) at the wound site of a murine excisional splint wound model. In this data article, we are providing the additional data of the reference article “Porous polymer scaffold for on-site delivery of stem cells – protects from oxidative stress and potentiates wound tissue repair” (Ramasatyaveni et al., 2016) [1]. This data consists of the characterization of bone marrow stem cells (BMSCs) showing the pluripotency and stem cell-specific surface markers. Image analysis of the cellular penetration into PEG–PU polymer network and the mechanism via enzymatic activation of MMP-2 and MMP-13 are reported. In addition, we provide a comparison of various routes of transplantation-mediated BMSCs engraftment in the murine model using bone marrow transplantation chimeras. Furthermore, we included in this dataset the engraftment of BMSCs expressing Sca-1+Lin−CD133+CD90.2+ in post-surgery day 10.

Pseudomonas aeruginosa biofilm is commonly associated with chronic wound infection. A FDA approved wireless electroceutical dressing (WED), which in the presence of conductive wound exudate gets activated to generate electric field (0.3-0.9V), was investigated for its anti-biofilm properties. Growth of pathogenic P. aeruginosa strain PAO1 in LB media was markedly arrested in the presence of the WED. Scanning electron microscopy demonstrated that WED markedly disrupted biofilm integrity in a setting where silver dressing was ineffective. Biofilm thickness and number of live bacterial cells were decreased in the presence of WED. Quorum sensing genes lasR and rhlR and activity of electric field sensitive enzyme, glycerol-3-phosphate dehydrogenase was also repressed by WED. This work provides first electron paramagnetic resonance spectroscopy evidence demonstrating that WED serves as a spontaneous source of reactive oxygen species. Redox-sensitive multidrug efflux systems mexAB and mexEF were repressed by WED. Taken together, these observations provide first evidence supporting the anti-biofilm properties of WED.