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Background: Derivation of hepatocytes from stem cells has been established through various protocols involving growth factor (GF) and small molecule (SM) agents, among others. However, mesenchymal stem cell-based derivation of hepatocytes still remains expensive due to the use of a cocktail of growth factors, and a long duration of differentiation is needed, thus limiting its potential clinical application., Methods: In this study, we developed a chemically defined differentiation strategy that is exclusively based on SM and takes 14 days, while the GF-based protocol requires 23-28 days., Results: We optimized a stage-specific differentiation protocol for the differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) into functional hepatocyte-like cells (dHeps) that involved four stages, i.e., definitive endoderm (DE), hepatic competence (HC), hepatic specification (HS) and hepatic differentiation and growth. We further generated hepatic tissue using human decellularized liver extracellular matrix and compared it with hepatic tissue derived from the growth factor-based protocol at the transcriptional level. dHep, upon transplantation in a rat model of acute liver injury (ALI), was capable of ameliorating liver injury in rats and improving liver function and tissue damage compared to those in the ALI model., Conclusions: In summary, this is the first study in which hepatocytes and hepatic tissue were derived from MSCs utilizing a stage-specific strategy by exclusively using SM as a differentiation factor., Competing Interests: Declarations Ethics Approval and Consent to Participate The patient(s) or their guardian(s)/legally authorized representative(s) provided written informed consent for participation in the study and/or the use of samples. Information regarding ethical approval as follows. Animal study: Title—“Development of vascularized liver tissue using Mesenchymal Stem Cells (MSCs) and HUVECs in decellularized liver biomatrix”, Approval no—IEC/2018/01/RSV-6/10 approved date – 15.07.2018. Human sample: Title – “Reengineering vascularized liver tissue using decellularized liver matrix”. Approval no – 03092018, Approval date – 04.09.2018. No clinical data from healthy or surviving liver ailment related patients were used in the study. Consent for Publication The study does not include person data in any form. Cadaveric liver organ was used in the present study and the ethical information approved by the institute has been included under the section “Animal and Human Ethics Approval” in the materials and method section. The patient(s) or their guardian(s)/legally authorized representative(s) provided written informed consent for participation in the study and/or the use of samples. Conflic of Interest The authors declare no conflicts of interest., (© 2024. The Author(s).)

The limited vanillin (3a) production from plant sources requires identifying some renewable and sustainable approaches for its synthesis. This study aimed to develop an efficient, eco-friendly process for synthesizing vanillin (3a) from eugenol (1a) and eugenol-rich essential oils. The chemical methodology for vanillin (3a) synthesis involved base-mediated isomerization of eugenol (1a) to isoeugenol (2a), followed by OsO 4 /NaIO 4 mediated oxidation of isoeugenol to vanillin (3a) using different additives such 1,4-diazabicyclo[2.2.2]octane (DABCO) and substituted pyridines in reusable environment-friendly solvents. Use of 2,6-dimethylpyridine and 2,6-dimethylpyridine N-oxide as additives in the oxidation step offered a significantly higher product yield (vanillin 3a, 70 %). The process synthesized vanillin (3a) irrespective of the cis/ trans stereochemistry of isoeugenol (2a). The peculiarity of the method relates to converting eugenol (1a) to vanillin (3a) without phenolic group protection, which offers step economy. Besides efficient vanillin (3a) synthesis, the process's general implications involve converting other naturally occurring phenylpropenes or phenylpropenes-enriched oils to the corresponding phenyl aldehydes (59-82 % yield)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The study examined the effects of herb drying, salt concentration, pH, and sampling approach on essential oil yield and composition in Pimenta dioica (L.) Merr. Fresh samples yielded higher essential oil (EO) (1.25%) than shade-dried ones. Increasing NaCl concentration correlated with higher EO yields, while a basic pH favoured superior yields. Gas Chromatography identified Eugenol and β-myrcene as primary constituents. Eugenol content peaked at 10% NaCl (56.429%) and was lowest at pH 4 (42.850%). β-myrcene content was highest at pH 4 (31.476%). Hydro distillation with systematic sampling evaluated the effects of 14 fractions in different time frames. Phenylpropanoids (mainly eugenol) and acyclic monoterpene (mainly β-myrcene) dominated all fractions, with cyclic monoterpene (mainly limonene) enriched in the first four fractions. Fractions 10 to 14 showed significant increases in eugenol compared to the control. These findings provide insights for meeting market demands, enhancing the commercial potential of P. dioica EO.

Magnetic skyrmions offer unique characteristics such as nanoscale size, particle-like behavior, topological stability, and low depinning current density. These properties make them promising candidates for next-generation spintronics-based memory and neuromorphic computing. However, one of their distinctive features is their tendency to deviate from the direction of the applied driving force that may lead to the skyrmion annihilation at the edge of nanotrack during skyrmion motion, known as the skyrmion Hall effect (SkHE). To overcome this problem, synthetic antiferromagnetic (SAF) skyrmions that having bilayer coupling effect allows them to follow a straight path by nullifying SkHE making them alternative for ferromagnetic (FM) counterpart. This study proposes an integrate-and-fire (IF) artificial neuron model based on SAF skyrmions with asymmetric wedge-shaped nanotrack having self-sustainability of skyrmion numbers at the device window. The model leverages inter-skyrmion repulsion to replicate the IF mechanism of biological neuron. The device threshold, determined by the maximum number of pinned skyrmions at the device window, can be adjusted by tuning the current density applied to the nanotrack. Neuronal spikes occur when initial skyrmion reaches the detection unit after surpassing the device window by the accumulation of repulsive force that result in reduction of the device's contriving current results to design of high energy efficient for neuromorphic computing. Furthermore, work implements a binarized neuronal network accelerator using proposed IF neuron and SAF-SOT-MRAM based synaptic devices for national institute of standards and technology database image classification. The presented approach achieves significantly higher energy efficiency compared to existing technologies like SRAM and STT-MRAM, with improvements of 2.31x and 1.36x, respectively. The presented accelerator achieves 1.42x and 1.07x higher throughput efficiency per Watt as compared to conventional SRAM and STT-MRAM based designs., (© 2024 IOP Publishing Ltd.)

Cymbopogon distans (Nees ex Steud.) Will. Watson (Poaceae) is a promising aromatic plant distributed in the Himalayas. In this study, five acyclic monoterpenoids, namely geranyl acetate (RS1), neral (RS2), geranial (RS3), citral (RS4) and geraniol (RS5) were isolated from the essential oil of C. distans . The isolated compounds were tested for in-vitro neuroinflammation inhibitory potential in LPS-stimulated BV2 microglial cells. RS1-RS4 exhibited significant neuroinflammation inhibition without any cytotoxic effect at the dose of 10 μM. RS4, the most active anti-neuroinflammatory compound (TNF-α 31.48 ± 1.00%; IL-6 24.02 ± 0.63%; IL-1β 42.15 ± 1.76%) was also able to inhibit acetylcholinesterase (AChE) in a dose-dependent manner. The results showed that RS4 (an isomeric mixture of neral and geranial) has the potential to inhibit neuroinflammation and AChE, which are the biomarkers of neurodegenerative disorders.

Zingiber zerumbet Sm. (Family: Zingiberaceae ) is an important perennial medicinal oil-bearing herb that is native to the Southeast Asia. This study examines the impact of different durations of post-harvest shade drying (ranging from 1 to 12 months) on essential oil yield and chemical composition of Z. zerumbet , in comparison to the freshly collected oil sample. This study explores how post-harvest shade drying impact the composition and longevity of Z. zerumbet rhizomes as well as its antimicrobial, antibiofilm activity. The oils were analyzed for their chemical composition analysis using a gas chromatography-flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The post-harvest periods of drying (1-12 months) were discovered to enhance the concentration of marker constituents in the oil. The primary constituent, Zerumbone, was detected in concentrations ranging from 69.38 ± 5.63% to a maximum of 80.19 ± 1.53% as the drying duration of the rhizome was extended. The output of the essential oil was not significantly affected by drying times; however, it did have a noticeable impact on the proportions of monoterpenes. Both disc diffusion and broth microdilution assay were used in freshly collected Z. zerumbet oil for its antimicrobial potential against S. aureus , L. monocytogens , S. hominis , Salmonella enterica serovar Typhimurium, P. aeruginosa , S. intermedius, E. coli , and C. albicans . For the first time, the oil reported to exhibit antibiofilm activity against S. aureus which was validated using fluorescence microscopy, and effectively disrupts the biofilm by 47.38% revealing that essential oil was able to disintegrate the clusters of the pathogen . Z. zerumbet rhizome oil is effective to reduce food-borne microorganisms. Therefore, its essential oil, a natural source of bioactive zerumbone, may improve flavor, aroma, and preservation., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© Prof. H.S. Srivastava Foundation for Science and Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Key Message: Thchit42 constitutive expression for fungal resistance showed synchronisation with leaf augmentation and transcriptome analysis revealed the Longifolia and Zinc finger RICESLEEPER gene is responsible for plant growth and development. Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed ~ 2fold increase in leaf size and ~ 2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, de novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and zinc finger (ZF) RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The preparation of 3-phosphorylated pyridines has remained the most challenging compared to the corresponding 2- or 4-functionalized pyridines. Herein, an unprecedented amino-organocatalyzed direct synthesis of 3-pyridylphosphonates from vinylphosphonates and aldehydes has been achieved. This allows access to a wide range of multi-substituted phosphorylated pyridines in excellent yields under transition metal-free conditions.

Metal/Metal Oxide nanoparticles (M/MO NPs) exhibit potential biomedical applications due to their tunable physicochemical properties. Recently, the biogenic synthesis of M/MO NPs has gained massive attention due to their economical and eco-friendly nature. In the present study, Nyctanthes arbor-tristis (Nat) flower extract-derived Zinc Ferrite NPs (Nat-ZnFe 2 O 4 NPs) were synthesized and physicochemically characterized by FTIR, XRD, FE-SEM, DLS, and other instruments to study their crystallinity, size, shape, net charge, presence of phytocompounds on NP's surface and several other features. The average particle size of Nat-ZnFe 2 O 4 NPs was approx. 25.87 ± 5.67 nm. XRD results showed the crystalline nature of Nat-ZnFe 2 O 4 NPs. The net surface charge on NPs was -13.28 ± 7.18 mV. When tested on mouse fibroblasts and human RBCs, these NPs were biocompatible and hemocompatible. Later, these Nat-ZnFe 2 O 4 NPs exhibited potent anti-neoplastic activity against pancreatic, lung, and cervical cancer cells. In addition, NPs induced apoptosis in tested cancer cells through ROS generation. These in vitro studies confirmed that Nat-ZnFe 2 O 4 NPs could be used for cancer therapy. Moreover, further studies are recommended on ex vivo platforms for future clinical applications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The topical application of essential oils is considered an effective treatment for skin diseases. Cymbopogon distans (Nees ex Steud.) Wats (Poaceae) is a promising aromatic grass widespread in the Himalayan temperate zone. Therefore, using in-vitro and in-vivo bioassays, we examined the chemical and pharmacological characteristics of essential oil hydro-distilled from C. distans coded as CDA-01, specifically concerning skin inflammation. Characterization using GC-FID and GC-MS provided a chemical fingerprint for CDA-01, enabling the identification of 54 compounds; amongst them, citral (34.3%), geranyl acetate (21.2%), and geraniol (16.4%) were the most abundant. To examine the anti-inflammatory potential, CDA-01 treatment on LPS-stimulated macrophage cells in addition to 12-O-tetradecanoylphorbol-13-acetate (TPA) generated cutaneous inflammatory reaction in the mouse ear was assessed through quantification of the inflammatory markers. Consequently, CDA-01 demonstrated protection against inflammation caused by LPS by lowering the pro-inflammatory cytokines (IL-6 and TNF-α) level in HaCaT cells with negligible cytotoxicity. Consistent with the in-vitro findings, CDA-01 treatment reduced pro-inflammatory mediators (TNF-, IL-6, and NO) and lipid peroxidation in an in-vivo investigation. Subcutaneous inflammation in TPA-treated mice ears was similarly decreased, as evidenced by the histological and morphological studies. As a result of our findings, it is possible that CDA-01 could be an effective treatment for skin inflammation disorders., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Inorganic nanoparticles (NPs) have played an important role as nano-drug delivery systems during cancer therapy in recent years. These NPs can carry cancer therapeutic agents. Due to this, they are considered a promising ancillary to traditional cancer therapies. Among inorganic NPs, Zinc Oxide (ZnO) NPs have been extensively utilized in cellular imaging, gene/drug delivery, anti-microbial, and anti-cancerous applications. In this study, a rapid and cost-effective method was used to synthesize Nat-ZnO NPs using the floral extract of the Nyctanthes arbor-tristis (Nat) plant. Nat-ZnO NPs were physicochemically characterized and tested further on in vitro cancer models. The average hydrodynamic diameter (Z average ) and the net surface charge of Nat-ZnO NPs were 372.5 ± 70.38 d.nm and -7.03 ± 0.55 mV, respectively. Nat-ZnO NPs exhibited a crystalline nature. HR-TEM analysis showed the triangular shape of NPs. Furthermore, Nat-ZnO NPs were also found to be biocompatible and hemocompatible when tested on mouse fibroblast cells and RBCs. Later, the anti-cancer activity of Nat-ZnO NPs was tested on lung and cervical cancer cells. These NPs displayed potent anti-cancer activity and induced programmed cell death in cancer cells., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Physiochemical properties of polycaprolactone-hydroxyapatite (PCL-HAp) composites were investigated in the pristine and after irradiation of γ rays (25, 50, 75, and 100 kGy). PCL-HAp composites were synthesized by solvent evaporation and characterized using spectroscopic methods as well as biological assays. The surface roughness (RMS) of the irradiated composite film (at 75 kGy) was 80 times higher than that of the pristine. Irradiation tailors the contact angle of the films from 77° to 90° (at 100 kGy). A decrease in particle size (at 100 kGy) of HAp nanorods in PCL-HAp composites film was observed. The XRD peak of PCL was slightly shifted from 21.2° to 21.7° (at 100 kGy) with the decrease in crystallite size. The peak intensity of the PCL and HAp altered on irradiation that was confirmed by FTIR and Raman analysis. Further, the bandgap of the irradiated film was lowered by 13 % (at 25 kGy). The luminescence intensity decreased due to the non-radiative process induced by the irradiation defects. All the samples possess hemocompatibility percentage of <10 % as per ASTM standards. At 75 kGy, fibroblast cell proliferation was higher than the pristine and other doses. The gamma-irradiated PCL-HAp composite films are potential candidates for tissue engineering applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Whole-organ re-engineering is the most challenging goal yet to be achieved in tissue engineering and regenerative medicine. One essential factor in any transplantable and functional tissue engineering is fabricating a perfusable vascular network with macro- and micro-sized blood vessels. Whole-organ development has become more practical with the use of the decellularized organ biomatrix (DOB) as it provides a native biochemical and structural framework for a particular organ. However, reconstructing vasculature and re-endothelialization in the DOB is a highly challenging task and has not been achieved for constructing a clinically transplantable vascularized organ with an efficient perfusable capability. Here, we critically and articulately emphasized factors that have been studied for the vascular reconstruction in the DOB. Furthermore, we highlighted the factors used for vasculature development studies in general and their application in whole-organ vascular reconstruction. We also analyzed in detail the strategies explored so far for vascular reconstruction and angiogenesis in the DOB for functional and perfusable vasculature development. Finally, we discussed some of the crucial factors that have been largely ignored in the vascular reconstruction of the DOB and the future directions that should be addressed systematically., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gupta, Sharma, Petrovski and Verma.)

Ethnobotanical Relevance: Rosa damascena Mill. (Rosaceae), commonly known as damask rose, is an ancient medicinal and perfumery plant used in Traditional Unani Medicine due to various therapeutic effects, including cardiovascular benefits., Aim of the Study: This study aimed to evaluate the vasorelaxant effect of the 2-phenyl ethyl alcohol (PEA) isolated from the spent flowers of R. damascena which remain after the extraction of essential oil., Materials and Methods: The freshly collected flowers of R. damascena were hydro-distilled in a Clevenger's type apparatus to extract the rose essential oil (REO). After removing the REO, the spent-flower hydro-distillate was collected and extracted with organic solvents to yield a spent-flower hydro-distillate extract (SFHE), which was further purified by column chromatography. The SFHE and its isolate were characterized by gas chromatography (GC-FID), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) techniques. The PEA, isolated from SFHE, was evaluated for vasorelaxation response in conduit blood vessels like rat aorta and resistant vessels like mesenteric artery. The preliminary screening of PEA was done in aortic preparation pre-constricted with phenylephrine/U46619. Further, a concentration-dependent relaxation response to PEA has been elicited in both endothelium-intact and endothelium-denuded arterial rings, and the mode of action was explored., Results: The SFHE revealed the presence of PEA as the main constituent (89.36%), which was further purified by column chromatography to a purity of 95.0%. The PEA exhibited potent vasorelaxation response both in conduit vessels like the rat aorta and resistance vessels like the mesenteric artery. The relaxation response is mediated without any involvement of vascular endothelium. Further, TEA sensitive BK C a channel was found to be the major target for PEA-induced relaxation response in these blood vessels., Conclusions: The spent flowers of R. damascena, which remain after the extraction of REO, could be used to extract PEA. The PEA possessed marked vasorelaxation properties in both aorta and mesenteric artery and showed promise for development into an herbal product against hypertension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Classical Hodgkin lymphoma represents a paradigm of tumor cell-microenvironment interactions as the neoplastic Hodgkin Reed-Sternberg (HRS) cells typically constitute less than 1% of the total tumor volume. CTLA-4, a member of the CD28/B7 immunoglobulin superfamily, and CD28 and their ligands B7-1 and B7-2 are critically important for the initial activation of naive T cells. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of the HL microenvironment. The study included 50 histopathological confirmed cases of Hodgkin lymphoma. IHC staining for CTLA-4 and B7-1 was performed on archival paraffin-embedded biopsy. SPSS version 17 was used for statistical analysis. CTLA-4 IHC expression in HRS cells was negative in all cases, while in immune cells, CTLA-4 expression was observed in 45 (90%) cases. CD80 expression was present in all cases, both in HRS and immune cells. There was a significant association between HRS cell percentage and IPS score (p-value=0.001). Mean survival duration was longer in <50% immune cells compared to >50% groups, with an overall mean survival of 67.633 months. Considering the CTLA4 expression in immune cells within the microenvironment and the availability of targeted drugs like Iplimumab, which act through CTLA4 blockade, it may be appropriate to use this as targeted therapy in HL cases, particularly in those with refractory disease who are unable to achieve cure prior to ASCT., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Cell therapy is one of the promising approaches for cardiac repair, subsequently after infarction or injury. However, contemporary mesenchymal stromal/stem cell (MSCs) delivery strategies result in low retention and poor engraftment of donor cells, thus limiting the therapeutic efficacy. Here, we developed an engineered biomimetic cardiogel patch (EBCP) comprising of the native decellularized cardiac extracellular matrix (ECM) "cardiogel" and chitosan, leading to the efficient regeneration of injured myocardium. We also developed novel bio-adhesive that is capable of suture-free epicardial placement of EBCP to injured myocardium. We have illustrated the potential of the mussels-inspired bioadhesive system, which comprises gelatin catechol and partially oxidized chitosan, which relies on self-crosslinking capability, to promote wet adhesion. In vitro studies with isolated cardiogel promoted cell proliferation, adhesion, and migration while aiding cardiomyogenic differentiation. The EBCP's ability to protect cells from abrasion due to surrounding tissues in the myocardial infarction (MI) rat model makes it more desirable. Furthermore, the epicardial implantation of the EBCP loaded with MSCs improves the initial retention of cells and subsequent functional cardiac recovery with enhanced myocardial tissue restoration. Histological examination showed the presence of EBCP and infiltration of cells to the infarcted heart tissue. The fast and facile synthesis of bioadhesive and major therapeutic benefits of EBCP make it a potential candidate for recuperating the ailing heart., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

N-(3-oxododecanoyl) homoserine lactone (3oc) is a Pseudomonas aeruginosa secreted quorum-sensing signal molecule playing a crucial role in regulating quorum-sensing (QS) dependent biofilm formation and secretion of virulence factors. In addition to regulating quorum sensing, 3oc also plays an immunomodulatory role in the host by triggering regulated cell death in immune cells. The molecular mechanisms of 3oc in modulating macrophage pathologies are still unclear. In this study, we hypothesized the novel 3oc mediated crosstalk between autophagy and apoptosis at the interphase of calcium signaling in human macrophages. The study showed that 3oc induces mitochondrial dysfunction and apoptosis in macrophages through elevating cytosolic Ca +2 ([Ca +2 ] cyt ) levels. Pre-treatment with the calcium-specific chelator BAPTA-AM effectively abrogated 3oc-induced apoptotic events, like mitochondrial ROS generation (mROS), mitochondrial membrane potential (MMP) drop, and phosphatidylserine (PS) exposure. The study also showed that 3oc induces autophagy, as assessed by the accumulation of autophagic vacuoles, induction of lysosomal biogenesis, upregulation of autophagy genes (LC3, BECLIN 1, STX17, PINK1, and TFEB), autophagosomes formation, and LC3 lipidation. Mechanistically, our study proved that 3oc-induced autophagy was [Ca +2 ] cyt dependent as BAPTA-AM pre-treatment reduced autophagosome formation. Furthermore, inhibiting autophagy with chloroquine attenuated 3oc-induced apoptosis, while autophagy induction with rapamycin aggravated cell death, suggesting autophagy plays a role in cell death in 3oc-treated macrophages. In conclusion, our findings indicate that 3oc activates a multifaceted death signaling by activating autophagy and apoptosis through Ca +2 signaling, and we propose pharmacological modulation of Ca +2 signaling may act as a combinatorial therapeutic intervention in patients with Pseudomonas aeruginosa-associated infections., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ravenia spectabilis Engl. belongs to the family Rutaceae is known to possess several biologically active phytomolecules. This study was planned to investigate the chemical composition and antimicrobial activity of the leaf essential oil of R. spectabilis . The hydrodistillation of fresh leaves of R. spectabilis gave 0.19 ± 0.02% essential oil. The resulting essential oil was analysed by gas chromatography-flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Altogether, thirty-one constituents forming 97.6 ± 1.72% of the total oil composition were identified. Major components of the oil were sabinene (60.8 ± 0.36%), α -pinene (5.4 ± 0.30%), myrcene (4.8 ± 0.25%), δ -3-carene (4.7 ± 0.62%) and β -pinene (4.3 ± 0.17%). The in-vitro antimicrobial potential of the oil was examined against eight human pathogenic bacterial and fungal strains. The essential oil showed significant activity against Staphylococcus aureus , Staphylococcus epidermidis , methicillin-resistant Staphylococcus aureus , methicillin-resistant Staphylococcus epidermidis , Candida albicans , and Candida kefyr . This is the first report on R. spectabilis leaf essential oil composition and its antimicrobial activity. The essential oil could be a promising natural source of sabinene and antimicrobial for developing new phytotherapeutics.

Parkinson's disease (PD) is a multifactorial ailment that severely affects the viability of dopaminergic neurons leading to progressive loss of motor control. The current regimen for PD treatment includes synthetic drugs that lack efficacy and cause serious side effects. Consequently, recent drug development studies are focusing on alternative medicines from plant sources. Artemisia pallens Wall. ex DC, commonly known as davana, is an annual aromatic herb cultivated in southern India. Given the diverse traditional and scientifically documented therapeutic effects of A. pallens, the pharmacological potential of the isolates of the plant, namely bicyclogermacrene (D1), cis-davanone (D3), and cis-hydroxy davanone (D5), was tested for anti-Parkinson's activity in Caenorhabditis elegans model. The tested compounds alleviated α-synuclein (α-syn) aggregation and maximum decline was observed in 25 μM D1 supplemented worms. Additionally, D1 modulated dopamine regulated nonanol-1 repulsion and locomotory behaviour of C. elegans validating its future use as a dopamine-enhancing agent. The genetic regulation mediating the above effects validated through the qPCR study showed that D1 supplementation displayed its anti-Parkinson's effect through upregulation of the antioxidant defence system genes (superoxide dismutase (sod)-1, sod-2, and sod-4) and PD associated pdr-1 gene that maintains the mitochondrial proteostasis. The molecular docking studies of C. elegans PDR-1 with D1 further confirmed its contribution in D1 induced abridgment of Parkinson disease linked pathologies in C. elegans disease model. Hence, this article proposes D1 as an effective regimen for curtailing the Parkinson disease linked pathologies through mechanism of maintaining cellular redox state and proteostasis., Competing Interests: Declaration of competing interest All the authors raise no conflict of interest concerning the contents presented in the current manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cymbopogon martini variety sofia, commonly known as ginger-grass, is an important aromatic crop used by the perfumery, medicinal and cosmetic industries worldwide. This study explores the chemical and possible pharmacological profile of hydro-distilled essential oil of C. martini variety sofia against skin inflammation. The essential oil extracted by the hydrodistillation process was analyzed by gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) to identify its constituents, and was coded as CMA-01 for further in vitro and in vivo pharmacological study related to skin inflammation. The chemical fingerprint revealed that CMA-01 oil has (E)-p-mentha-2,8-dien-1-ol (21.0%), (E)-p-mentha-1(7),8-dien-2-ol (18.1%), (Z)-p-mentha-1(7),8-dien-2-ol (17.4%), (Z)-p-mentha-2,8-dien-1-ol (9.0%), limonene (7.7%), and (E)-carveol (5.7%) as major components. The pre-treatment of CMA-01 showed significant inhibition of pro-inflammatory markers in activated HaCat cells without cytotoxic effect. The in vivo study revealed the ameliorative impact of CMA-01 against skin inflammation induced by TPA in mouse ears as evidenced by a reduction of ear edema, pro-inflammatory mediators (IL-6, TNF-α), oxidative stress markers (malondialdehyde and nitric-oxide) and histological changes in ear tissues without any skin irritation response on rabbit skin. These findings suggest the suitability of CMA-01 as a valuable therapeutic candidate for the treatment of skin inflammation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Irreversible myocardium infarction is one of the leading causes of cardiovascular disease (CVD) related death and its quantum is expected to grow in coming years. Pharmacological intervention has been at the forefront to ameliorate injury-related morbidity and mortality. However, its outcomes are highly skewed. As an alternative, stem cell-based tissue engineering/regenerative medicine has been explored quite extensively to regenerate the damaged myocardium. The therapeutic modality that has been most widely studied both preclinically and clinically is based on adult multipotent mesenchymal stem cells (MSC) delivered to the injured heart. However, there is debate over the mechanistic therapeutic role of MSC in generating functional beating cardiomyocytes. This review intends to emphasize the role and use of MSC in cardiac regenerative therapy (CRT). We have elucidated in detail, the various aspects related to the history and progress of MSC use in cardiac tissue engineering and its multiple strategies to drive cardiomyogenesis. We have further discussed with a focus on the various therapeutic mechanism uncovered in recent times that has a significant role in ameliorating heart-related problems. We reviewed recent and advanced technologies using MSC to develop/create tissue construct for use in cardiac regenerative therapy. Finally, we have provided the latest update on the usage of MSC in clinical trials and discussed the outcome of such studies in realizing the full potential of MSC use in clinical management of cardiac injury as a cellular therapy module., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fluid shear stress (FSS) is crucial in cancer cell survival and tumor development. Noteworthily, cancer cells are exposed to several degrees of FSS in the tumor microenvironment and during metastasis. Consequently, the stemness marker expression in cancer cells changes with the FSS signal, although it is unclear how it varies with different magnitudes and during metastasis. The current work explores the stemness and drug resistance characteristics of the cervical cancer cell line HeLa in a microfluidic device with a wide range of physiological FSS. Hence, the microfluidic device was designed to achieve a logarithmic flow distribution in four culture chambers, realizing four orders of biological shear stress on a single chip. The cell cycle analysis demonstrated altered cell proliferation and mitotic arrest after FSS treatment. In addition, EdU staining revealed increased cell proliferation with medium to low FSS, whereas high shear had a suppressing effect. FSS increased competence to withstand higher intracellular ROS and mitochondrial membrane potential in HeLa. Furthermore, stemness-related gene (Sox2, N-cadherin) and cell surface marker (CD44, CD33, CD117) expressions were enhanced by FSS mechanotransduction in a magnitude-dependent manner. In summary, these stemness-like properties were concurrent with the drug resistance capability of HeLa towards doxorubicin. Overall, our microfluidic device elucidates cancer cell survival and drug resistance mechanisms during metastasis and in cancer relapse patients.

Successful regeneration of load-bearing bone defects remains a major challenge in clinical orthopaedics. Designing biologically active 3-dimensional scaffolds possessing physiological responsiveness can potentially overcome current limitations. Here, we have described a novel approach to fabricate scaffolds with modified nanosheets reinforced on mechanically customized thermoplastic polymer-based 3D printed constructs. In this article, we have developed polydopamine-reduced graphene oxide (PD-RGO) reinforced 3D printed PLA scaffold for bone tissue construction. RGO was synthesized by reduction of GO under alkaline conditions using dopamine. 3D printed polylactic acid (PLA) scaffold with defined porosity was doped with PD-RGO. The designed scaffold was studied for its physiochemical properties and human umbilical cord-derived mesenchymal stem cell (hMSC) behaviour within the scaffold. In vitro hMSC studies revealed the influence of fibre direction and nanocoating on directional cell growth and proliferation. The fabricated scaffold showed antioxidant property along with pro-angiogenic and osteoinductive potential. The designed scaffold also successfully prevented the formation of biofilm. In vivo heterotopic implantation of the differentiated hMSC loaded scaffold confirmed the biocompatibility and bio functionality of the scaffold. In summary, the designed nanoplates doped 3D printed scaffold displays stem cell responsive, integrative and pro-regenerative multi functionalities, thereby, exhibiting potential application as bone tissue regeneration treatment alternative., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Liver failure is a critical disease for which regenerative therapies are still being explored. The major limitation in the use of a clinical grade, viable cell-based therapy approach is the scarce availability of sufficient number of in-vitro differentiated hepatocyte-like cells (HLC) that can induce regeneration and ameliorate liver injury. Here, we report for the first time an approach to engineer HLCs using sera of hyperbilirubin patients that act as a reservoir of differentiation factor. Utilizing our humanized approach, mesenchymal stem cells (hMSC) derived from umbilical cord tissue were transdifferentiated into HLC using patient-derived serum along with dimethyl sulfoxide (DMSO). We studied the effects of serum on the proliferation, cell cycle analysis, and apoptosis of hMSC by various differentiation combinations. We optimized the hepatic transdifferentiation ability of hMSC with hyperbilirubin serum treatment for a period of 7 days. Assessment of HLC functionalities was shown by quantifying the HLC spent medium for albumin and urea secretions. Transplantation of HLC in an acute liver injury (ALI) rat model showed an effective improvement in the liver function and histological changes in the liver. The results of this study suggest that hMSC-derived HLC using humanized hepatogenic serum holds a promising potential for cell transplantation, as an efficient therapy modality for liver failure in humans., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mesenchymal stromal cells (MSCs) are very advantageous in the field of regenerative medicine because of their immunomodulatory properties. However, reports show that these properties vary from source to source. Hence, understanding the source-dependent specificity of MSCs and their immunomodulatory abilities will enable optimal use of MSCs in cell-based therapies. Here, we studied human MSCs from three different sources, adipose tissue (AT), bone marrow (BM) and Wharton's jelly (WJ), with respect to phenotypic responses of human peripheral blood mononuclear immune cells (hPBMCs/MNCs) and the concurrent changes in cytokine expression in MSCs, under mitogen-stimulated co-culture conditions. We used cytometric analysis to study the immunoregulatory properties of MSCs on MNCs and cytokine profiling of MSCs using a customized PCR array and solid-phase sandwich enzyme-linked immunosorbent assay. Our results reveal differential modulation of immune cells as well as MSCs upon activation by the mitogen phytohemagglutinin, independently and in co-culture. Notably, we observed source-specific MSC-cytokine signatures under stimulated conditions. Our results show that AT-MSCs up-regulate VEGF, BM-MSCs up-regulate PTGS-2 and WJ-MSCs increase expression of IDO considerably compared with controls. This remarkable modulation in source-specific cytokine expression was also validated at a functional level by quantitative protein expression studies. In our hands, even though MSCs from AT, BM and WJ sources exhibit characteristic immunomodulatory properties, our results highlight that MSCs sourced from different tissues may exhibit unique cytokine signatures and thus may be suitable for specific regenerative applications., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2021. Published by Elsevier Inc.)

Mesenchymal stem cells (MSCs) differentiation toward cardiovascular lineage prediction using the global methylome profile will highlight its prospective utility in regenerative medicine. We examined the propensity prediction to cardiovascular lineage using 5-Aza, a well-known cardiac lineage inducer. The customized 180 K microarray was performed and further analysis of global differentially methylated regions by Ingenuity pathway analysis (IPA) in both MSCs and 5-AC-treated MSCs. The cluster enrichment tools sorted differentially enriched genes and further annotated to construct the interactive networks. Prediction analysis revealed pathways pertaining to the cardiovascular lineage found active in the native MSCs, suggesting its higher propensity to undergo cardiac, smooth muscle cell, and endothelial lineages in vitro. Interestingly, gene interaction network also proposed majorly stemness gene network NANOG and KLF6 , cardiac-specific transcription factors GATA4, NKX2.5 , and TBX5 were upregulated in the native MSCs. Furthermore, the expression of cardiovascular lineage specific markers such as Brachury, CD105, CD90, CD31 , KDR and various forms of ACTIN (cardiac, sarcomeric, smooth muscle) were validated in native MSCs using real time PCR and immunostaining and blotting analysis. In 5-AC-treated MSCs, mosaic interactive networks were observed to persuade towards osteogenesis and cardiac lineage, indicating that 5-AC treatment resulted in nonspecific lineage induction in MSCs, while MSCs by default have a higher propensity to undergo cardiovascular lineage., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-03058-2., Competing Interests: Competing interestsThe authors declare no competing interests., (© King Abdulaziz City for Science and Technology 2021.)

Artemisia pallens Wall. ex DC., popularly known as davana, has gained considerable attention because of its unique fragrance, high economic value, and pharmacological properties. The compositional complexity of davana essential oil (DO) has been a challenge for quality control. In this study, the chemical profile of DO was developed using polarity-based fractionation and a combination of gas chromatographic (GC-FID), hyphenated chromatographic (GC/MS), and spectroscopic (Fourier-Transform Infra-Red, 1D, 2D-Nuclear Magnetic Resonance) techniques. The analysis led to the identification of ninety-nine compounds. Major components of the DO were cis-davanone (D3, 53.0 %), bicyclogermacrene (6.9 %), trans-ethyl cinnamate (4.9 %), davana ether isomer (3.4 %), spathulenol (2.8 %), cis-hydroxy davanone (2.4 %), and trans-davanone (2.1 %). The study led to identifying several co-eluting novel minor components, which could help determine the authenticity of DO. The rigorous column-chromatography led to the isolation of five compounds. Among these, bicyclogermacrene, trans-ethyl cinnamate, and spathulenol were isolated and characterized by spectroscopic methods for the first time from DO. Pharmacological profile revealed that the treatment of DO and D3 inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6) induced by lipopolysaccharide (LPS) in primary macrophages without any cytotoxic effect after administration of their effective concentrations. The result of this study indicates the suitability of DO and D3 for further investigation for the treatment of chronic skin inflammatory conditions., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Mesenchymal stem cells (MSCs) are so far the most widely researched stem cells in clinics and used as an experimental cellular therapy module, particularly in cardiac regeneration and repair. Ever since the discovery of cardiomyogenesis induction in MSCs, a wide variety of differentiation protocols have been extensively used in preclinical models. However, pre differentiated MSC-derived cardiomyocytes have not been used in clinical trials; highlighting discrepancies and limitations in its use as a source of derived cardiomyocytes for transplantation to improve the damaged heart function. Therefore, this review article focuses on the strategies used to derive cardiomyocytes-like cells from MSCs isolated from three widely used tissue sources and their differentiation efficiencies. We have further discussed the role of MSCs in inducing angiogenesis as a cellular precursor to endothelial cells and its secretory aspects including exosomes. We have then discussed the strategies used for delivering cells in the damaged heart and how its retention plays a critical role in the overall outcome of the therapy. We have also conversed about the scope of the local and systemic modes of delivery of MSCs and the application of biomaterials to improve the overall delivery efficacy and function. We have finally discussed the advantages and limitations of cell delivery to the heart and the future scope of MSCs in cardiac regenerative therapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Surgical sutures are the most widely used medical device in any surgical procedure worldwide. In this study, modified electrospinning technique has been used as manufacturing technique to produce nanofiber bundles twisted simultaneously to obtain nanofiber yarns. Taking the advantage of nanofiber yarns in terms of biomimetic structure, mechanical strength and handling properties, the material is chosen. Curcumin, a natural compound is incorporated to the nanofiber yarns by blend electrospinning technique for its anti-inflammatory, antibiotic and wound healing properties. The synthesized nanofiber yarns were characterized by various characterization techniques such as XRD, FTIR, SEM, Tensile testing, stem cell interaction, hemocompatibility, bacterial response, drug release profiling and in vivo studies. Curcumin loaded nanofiber yarns demonstrated sustained release with improved antibacterial, antiplatelet, cell migration and stem cell interaction in vitro. The results from skin inflammation animal model revealed that curcumin laden nanofiber yarn suture manifested reduced inflammation and cellularity. The three dimensional structure, adequate mechanical strength and biological properties of the nanofiber yarn provide naive environment for wound healing with the balanced degradation of suture material in rat model., (Copyright © 2021 Elsevier B.V. All rights reserved.)