Synergistic effect of polymer functionalized graphene oxide system for breast cancer treatment.

The multifaceted drug carrier system is an emerging trend in delivering chemotherapeutic drugs and photosensitizers for the synergistic effect. In this work, we have designed a functionalized graphene oxide (GO) based carrier system for combined chemo-photodynamic therapeutic effects. Doxorubicin (DOX) and rose bengal (RB) were entrapped on the surface of GO via hydrophobic and π-π stacking interactions. The functional group determination, crystalline properties, surface morphology, and hydrodynamic size were evaluated using FT-IR, XRD, SEM, TEM, AFM, and DLS analysis. At 24 h, the entrapment efficiency was 65 % DOX and 40.92 % RB, and the loading capacities were 16.9 % DOX and 5.68 % RB observed at 30 min. The drug release percentage was higher in pH-2.6 rather than in pH-5.5, 6.8, and 7.4 pH environments. The in-vitro toxicity analysis using the LDH assay reveals that the DOX and RB co-loaded carriers had a significant cytotoxic effect on MCF-7 cells, indicating that the carrier could improve the therapeutic efficacy of DOX. Morphological changes were studied using inverted light microscopy; the cells were irradiated with a laser 525 nm 10 J/cm2 for 2 min 51 sec, and it was observed that the DOX and RB co-loaded carrier with laser-irradiated cells exposed the high-level morphological changes with the occurrence of apoptotic cell death. Compared to free DOX, the DOX/RB co-loaded carrier + laser had an efficient anticancer activity, as confirmed by DAPI staining cell uptake, flow cytometry, and intracellular ROS generation analysis. The DOX and RB co-loaded carrier clearly exhibits the RB-mediated photodynamic action on MCF-7 cells in response to external laser light irradiation. It permits an on-demand dual-payload release to trigger an instantaneous photodynamic and chemo treatment for cancer cell eradication. Finally, the ensuing dual-agent release is probable to successfully fight cancer via a synergistic effect.

Hyperandrogenism diminishes maternal-fetal fatty acid transport by increasing FABP4-mediated placental lipid accumulation†.

Long-chain polyunsaturated fatty acids (LCPUFAs) are critical for fetal brain development. Infants born to preeclamptic mothers or those born growth restricted due to placental insufficiency have reduced LCPUFA and are at higher risk for developing neurodevelopmental disorders. Since plasma levels of testosterone (T) and fatty acid-binding protein 4 (FABP4) are elevated in preeclampsia, we hypothesized that elevated T induces the expression of FABP4 in the placenta leading to compromised transplacental transport of LCPUFAs. Increased maternal T in pregnant rats significantly decreased n-3 and n-6 LCPUFA levels in maternal and fetal circulation, but increased their placental accumulation. Dietary LCPUFAs supplementation in T dams increased LCPUFA levels in the maternal circulation and further augmented placental storage, while failing to increase fetal levels. The placenta in T dams exhibited increased FABP4 mRNA and protein levels. In vitro, T dose-dependently upregulated FABP4 transcription in trophoblasts. Testosterone stimulated androgen receptor (AR) recruitment to the androgen response element and trans-activated FABP4 promoter activity, both of which were abolished by AR antagonist. Testosterone in pregnant rats and cultured trophoblasts significantly reduced transplacental transport of C14-docosahexaenoic acid (DHA) and increased C14-DHA accumulation in the placenta. Importantly, FABP4 overexpression by itself in pregnant rats and trophoblasts increased transplacental transport of C14-DHA with no significant placental accumulation. Testosterone exposure, in contrast, inhibited this FABP4-mediated effect by promoting C14-DHA placental accumulation.

Methotrexate related cutaneous adverse drug reactions: a systematic literature review.

OBJECTIVES: Recently, there is an increased number of reports being published on Methotrexate (MTX) related cutaneous manifestations. We aimed to identify and critically appraise descriptive studies describing the MTX related skin manifestations, treatment approach, and their outcomes. METHODOLOGY: An extensive literature search was performed in the PubMed, Embase, and Scopus databases from inception to April 2021 without any restrictions along with the bibliographic search of included studies, grey literature search, and a snowball search was performed in Google and Google Scholar to identify the relevant literature. Descriptive studies reporting MTX related cutaneous manifestations were considered for the review. The study selection, data extraction, and quality assessment were conducted by two independent reviewers and any disagreements were settled by consensus with the third reviewer. RESULTS: 31 out of 8,365 descriptive studies including 38 patients (22 females and 16 males) aged between 12 and 78 years prescribed for the management of rheumatoid arthritis, ankylosing spondylitis, and psoriasis were included in this review. Toxic epidermal necrolysis (TEN), papular eruption, vasculitis, erosions of psoriasis, ulcerated psoriatic plaques, local reactions, keratinocyte dystrophy, erythema multiforme, drug rash with eosinophilia and systemic symptoms, Steven Johnson syndrome and photosensitive dermatitis were the majority of MTX induced cutaneous reactions. Immediate withdrawal of MTX, providing appropriate care with anti-inflammatory, topical steroids, and supplementation with folic acid were reported to be effective for the management of the MTX related cutaneous manifestations. CONCLUSIONS: Clinicians and healthcare professionals should be aware of possible acute cutaneous drug reactions induced by MTX to avoid further consequences and fatal conditions. Immediate withdrawal of MTX and supportive care were reported as an efficacious therapeutic management of acute cutaneous drug reactions. PROSPERO REGISTRATION NUMBER: CRD42020220038.

Role of photobiomodulation on the activation of the Smad pathway via TGF-ß in wound healing.

Wound healing is an essential process in which the separated or destroyed tissue attempts to restore itself into its normal state. In some instances, healing is prolonged and remains stagnant in the inflammatory phase, and is referred to as a chronic wound. At a cellular and molecular level, many factors are required during the process of successful wound healing, such as cytokines, polypeptide growth factors and components of the extracellular matrix (ECM). Transforming growth factor-beta (TGF-ß) is considered as one of the essential growth factors in wound healing. Working through the Smad pathway, it is the main inducer of fibroblast differentiation which is essential for wound healing. Photobiomodulation (PBM) shows significant advantages in wound healing, and may stimulate cellular processes and tissue regeneration that results in an increase in growth factors and a decrease in inflammatory cytokines. Moreover, it leads to enhanced cell proliferation, migration, angiogenesis, and increased adenosine triphosphate (ATP) and cytochrome C oxidase (CCO) activity. In this review paper, we discuss the effects of PBM and its role on the activation of the TGF-ß/Smad pathway in the process of wound healing.

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

Cellular imaging and bactericidal mechanism of green-synthesized silver nanoparticles against human pathogenic bacteria.

In recent years, silver nanoparticles (AgNPs) have attracted significant attention in medicinal, biomedical, and pharmaceutical research owing to their valuable physicochemical and antibacterial properties. Leaf sap extract (LSE) from Aloe arborescens can be used as an active ingredient for different biological applications, including wound healing. In this study, we have investigated the use of LSE from A. arborescens as a reducing, stabilizing and capping agent to produce AgNPs during the so called "green synthesis" (G-AgNPs). The objective of this study was to prepare, characterize and evaluate the potential of G-AgNPs against human pathogenic bacteria for the intended use as treatment of infected wounds. When the mixture of silver nitrate solution and LSE was exposed to direct sunlight it yielded a rapid color change from colorless to reddish-brown, indicating the formation of G-AgNPs. Physicochemical characterization such as Single particle inductively coupled plasma mass spectrometry, High resolution transmission electron microscopy and surface chemistry studies (Fourier transform infrared spectroscopy and X-Ray diffraction) revealed a small size in the range of 38±2nm, smooth surface and existence of LSE on the G-AgNPs. G-AgNPs possessed good antibacterial activity against both Pseudomonas aeruginosa and Staphylococcus aureus. The flow cytometry study revealed the increased percentage of dead cells treated by G-AgNPs through cell membrane damage, and it was further confirmed by confocal laser scanning microscopy. Thus, the present study reveals that the novel G-AgNPs demonstrated effective antibacterial properties against both Gram-negative and Gram-positive bacterial strains and shows great potential for its use in the treatment of pathogen infected wounds.

Cryosupernatant and Immunosuppression as Effective Alternative Therapies for TTP in Three Pediatric SLE Patients.

Thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE) very rarely present simultaneously and pose a diagnostic and therapeutic dilemma to the physician. Prompt diagnosis and management with plasma exchange and immunosuppression is life-saving. To describe the effectiveness of cryosupernatant and steroids in pediatric SLE with TTP. We describe three children aged 12-14 years with SLE who were diagnosed with TTP based on fever, CNS manifestations, ANA, anti-dsDNA, anti-sm positivity, hypocomplementemia, and microangiopathic anemia with thrombocytopenia. All three children were managed with cryosupernatant and steroids without plasmapheresis. All children improved with cryosupernatant and steroids. All attained remission within 10 days. They were doing well at last follow up without relapse or flare. Cryosupernatant and steroids may be an effective therapy for Thrombotic thrombocytopenic purpura with systemic lupus erythematosus.

Awareness of basic life support among medical, dental, nursing students and doctors.

To study the awareness of Basic Life Support (BLS) among students, doctors and nurses of medical, dental, homeopathy and nursing colleges. A cross-sectional study was conducted by assessing responses to 20 selected basic questions regarding BLS among students, doctors and nurses of medical, dental, homeopathy and nursing colleges. After excluding the incomplete response forms the data was analysed on 1,054 responders. The results were analysed using an answer key prepared with the use of the Advanced Cardiac Life Support manual. Out of 1,054 responders 345 were medical students, 75 were medical interns, 19 were dental students, 59 were dental interns, 105 were homeopathy interns, 319 were nursing students, 72 were doctors, 29 were dentists, 25 were nursing faculty and six were homeopathy doctors. No one among them had complete knowledge of BLS. Only two out of 1054 (0.19%) had secured 80 - 89% marks, 10 out of 1054 (0.95%) had secured 70 - 79% marks, 40 of 1054 (4.08%) had secured 60 - 69% marks and 105 of 1054 (9.96%) had secured 50 - 59% marks. A majority of them, that is, 894 (84.82%) had secured less than 50% marks. Awareness of BLS among students, doctors and nurses of medical, dental, homeopathy and nursing colleges is very poor.