Exploring Flower-Structured Bifunctional VCu Layered Double Hydroxide and its Nanohybrid with g-C3N4 for Electrochemical and Photoelectrochemical Seawater Electrolysis.

Seawater electrolysis holds great promise for sustainable green hydrogen generation, but its implementation is hindered by high energy consumption and electrode degradation. Two dimensional (2D) layered double hydroxide (LDH) exhibits remarkable stability, high catalytic activity, and excellent corrosion resistance in the harsh electrolytic environment. The synergistic effect between LDH and seawater ions enhances the oxygen evolution reaction, enabling efficient and sustainable green hydrogen generation. Here, we report a synthesis of low cost, novel 2D Vanadium Copper (VCu) LDH first time in the series of LDH's as a highly efficient bifunctional electrocatalyst. The electrochemical (EC) and photoelectrochemical (PEC) study of VCu LDH and VCu LDH/Graphite Carbon Nitride (g-C3N4) nanohybrid was performed in 0.5 M H2SO4 (acidic), 1 M KOH (basic), 0.5 M NaCl (artificial seawater), 0.5 M NaCl + 1 M KOH (artificial alkaline seawater), real seawater and 1 M KOH + real seawater (alkaline real seawater) electrolyte medium. It was found that VCu LDH shows a remarkable lower overpotential of 72 mV hydrogen evolution reaction (HER) and 254 mV oxygen evolution reaction (OER) at current density of 10 mA/cm2 under alkaline real seawater electrolysis exhibiting bifunctional activity and also showing better stability.

Assessing Residents in the Department of Surgery at a Tertiary Care Centre Using Mini-Clinical Evaluation Exercise (Mini-CEX).

OBJECTIVE: This study aimed to introduce, sensitize, and train our postgraduate students and faculty of the department of general surgery with the use of mini-Clinical Evaluation Exercise (mini­CEX) and to assess the perception of students and faculty towards it. MATERIAL AND METHODS: A cross­sectional observational study was conducted over a period of four months. Ten surgery residents in the department were asked to volunteer to participate and five professors conducted the session. Five sessions of mini­CEX (nine points) were conducted for each resident in different settings of the out­patient department (OPD) and in­patient department (IPD). A total of five skills were tested. Feedback from faculty and residents regarding the perception of mini­CEX was also taken. RESULTS: A statistically significant difference in mean scores of all domains was observed comparing the first and last assessment (p<0.05). Hundred percent of the residents scored superior category (7-9) in the final assessment in all domains, whereas the maximum was in a satisfactory scoring grade in 1st assessment. The time taken for the assessment significantly reduced from 1st assessment to the last assessment in OPD and IPD settings (p=0.001). The mini-CEX assessment tool got 100% feedback from faculty in terms of skill improvement, method, attitude of residents, and ability to identify gaps in knowledge. However, one assessor thought that "time given for assessment" was inadequate and more effort was required than the usual traditional assessment methods. The most identified problem faced by residents was that the "time given during assessment" was less (50%); however, overall residents also found it valid, effective, and helpful in identifying knowledge gaps and improving clinical and communication skills. CONCLUSION: Mini­CEX improves the learning environment in residency and also leads to improvement in medical interviewing skills, physical examination skills, humanistic qualities/professionalism, and counseling skills. So, it can be used for residency training in clinical departments.

Characterizing morphological alterations in blood related disorders through Atomic Force Microscopy.

Atomic Force Microscopy (AFM) is a very flexible method that can create topographical images from a range of materials and image surfaces. Significantly, AFM has emerged as an invaluable tool for dissecting the morphology and biochemical aspects of body cells and tissues. The high-resolution imaging capabilities of AFM enable researchers to discern alterations in cell morphology and understand the underlying mechanisms of diseases. It contributes to understanding disease etiology and progression. In the context of this review, our focus will be directed towards elucidating the pivotal role of AFM in analysis of blood related disorders. Through detailed comparisons with normal cells, we delve into the alterations in size, shape, and surface characteristics induced by conditions such as cancer, diabetes, anaemia, and infections caused by pathogens. In essence, various work described in this article highlights to bridge the gap between traditional microscopy and in-depth analysis of blood-related pathologies, which in turn offers valuable perspectives for both research and clinical applications in the field.

Development of injectable upconversion nanoparticle-conjugated doxorubicin theranostics electrospun nanostructure for targeted photochemotherapy in breast cancer.

Nanotheranostic-based photochemotherapies with targeted drug delivery have considerably surfaced in cancer therapy. In the presented work, polyethyleneimine-coated upconversion nanoparticles were engineered to conjugate covalently with doxorubicin. Upconversion nanoparticles (UCNP)-Doxorubicin (DOX)/synthesized epidermal growth factor receptor-targeting peptide blended with polymer composite was electrospun and formulated as the injectable dosage form. The size of the UCNP and the nanofiber diameter were assessed as 26.75 ± 1.54 and 162 ± 2.82 nm, respectively. The optimized ratio of dopants resulted in UCNP photoluminescence with maximum emission intensity at around 800 nm upon 980 nm excitation wavelength. The paramagnetic nature of UCNPs and amide conjugation with the drug was confirmed analytically. The loading capacity of UCNP for doxorubicin was determined to be 54.56%, while nanofibers exhibited 98.74% capacity to encapsulate UCNP-DOX. The release profile of UCNP-DOX from nanofiber formulation ranged from sustained to controlled, with relative enhancement in acidic conditions. The nanofiber demonstrated good mechanical strength, robust swelling, and degradation rate. Biocompatibility tests showed more than 90% cell viability on L929 and NIH/3T3 cell lines with UCNP-DOX@NF/pep nanoformulation. The IC50 values of 2.15 ± 0.54, 2.87 ± 0.67, and 3.42 ± 0.45 µg/mL on MDA-MB-231, 4T1, and MCF-7 cancer cell line, respectively, with a significant cellular uptake, has been reported. The UCNP protruded a ≈62.7°C temperature rise within 5 min of 980 nm laser irradiation and a power density of 0.5 W cm-2. The nanoformulation induced reactive oxygen species of 65.67% ± 3.21% and apoptosis by arresting the cell cycle sub-G1 phase. The evaluation conveys the effectiveness of the developed injectable theranostic delivery system in cancer therapy.

Surface engineered nanohybrids in plasmonic photothermal therapy for cancer: Regulatory and translational challenges.

Plasmonic materials as non-invasive and selective treatment strategies are gaining increasing attention in the healthcare sector due to their remarkable optical and electronic properties, where the interface between matter and light becomes enhanced and highly localized. Some attractive applications of plasmonic materials in healthcare include drug delivery to target specific tissues or cells, hence reducing the side effects of the drug and improving their efficacy; enhancing the contrast and resolution in bioimaging; and selectively heating and destroying the cancerous cells while parting the healthy cells. Despite such advancements in photothermal therapy for cancer treatment, some limitations are still challenging. These include poor photothermal conversion efficiency, heat resistance, less accumulation in the tumor microenvironment, poor biosafety of photothermal agents, damage to the surrounding healthy tissues, post-treatment inflammatory responses, etc. Even though the clinical application of photothermal therapy is primarily restricted due to poor tissue penetration of excitation light, enzyme therapy is hindered due to less therapeutic efficacy. Several multimodal strategies, including chemotherapy, radiotherapy, photodynamic therapy, and immunotherapy were developed to circumvent these side effects associated with plasmonic photothermal agents for effective mild-temperature photothermal therapy. It can be prophesied that the nanohybrid platform could pave the way for developing cutting-edge multifunctional precise nanomedicine via an ecologically sustainable approach towards cancer therapy. In the present review, we have highlighted the significant challenges of photothermal therapy from the laboratory to the clinical setting and their struggle to get approval from the Food and Drug Administration (FDA).

Wearable sweat chloride sensors: materials, fabrication and their applications.

Chloride is a crucial anion required for multiple functions in the human body including maintaining acid-base balance, fluid balance, electrical neutrality and supporting muscles and nerve cells. Low-chloride levels can cause nausea, diarrhoea, etc. Chloride levels are measured in different body fluids such as urine, serum, sweat and saliva. Sweat chloride measurements are used for multiple applications including disease diagnosis, sports monitoring, and geriatric care. For instance, a sweat chloride test is performed for cystic fibrosis screening. Further, sweat also offers continuous non-invasive access to body fluids for real-time monitoring of chloride that could be used for sports and geriatric care. This review focuses on wearable chloride sensors that are used for periodic and continuous chloride monitoring. The multiple sections in the paper discuss the clinical significance of chloride, detection methods, sensor fabrication methods and their application in cystic fibrosis screening, sports and geriatric care. Finally, the last section discusses the limitation of current sensors and future directions for wearable chloride sensors.

A Systematic Narrative Review on ADIPOQ Gene Variants and its Association with T2DM in the Indian Population.

BACKGROUND: The prevalence of diabetes is rapidly increasing in India, even among young adult individuals. Rare adiponectin gene (ADIPOQ) variants may be predominantly present in Indians and decrease the circulatory levels of APN (Adiponectin). Studies reported that ADIPOQ gene variants were associated with type 2 diabetes mellitus (T2DM) and its complications in the Indian population. OBJECTIVES: To review the association of specific ADIPOQ gene variants with T2DM and its associated complications. MATERIALS & METHODS: A search of Pubmed, Chinhal, Medline, Scopus, Web of Science databases, and Google Scholar search engine was performed to retrieve articles by using the following keywords; "ADIPOQ and T2DM", "ADIPOQ and India," "ADIPOQ gene variants and T2DM", "ADIPOQ gene variants and T2DM and India", "SNPs of ADIPOQ gene and T2DM", "SNPs of ADIPOQ gene and India," SNPs of ADIPOQ gene and T2DM and India". Eligibility criteria for the inclusion of articles: Original, Case-Control Study, and Full-Text articles were published in the English language till the end of April 2023. RESULTS: A total of 540 articles were retrieved. Out of this, only 18 articles were found suitable to include in this systematic narrative review. The most studied ADIPOQ gene variants were found to be +10211T/G (rs17846866), +45T/G (rs2241766), and +276G/T (rs1501299) in different Indian populations. CONCLUSION: It was reviewed that ADIPOQ gene variants +10211T/G (rs17846866), +45T/G (rs2241766), and +276G/T (rs1501299) were predominantly present in the Indian population, and decreasing the circulatory levels of APN and significantly associated with T2DM and its complications.

A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

BACKGROUND & AIMS: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To develop new therapeutic strategies for these patients, our laboratory has developed a preclinical testing pipeline. Given that histone deacetylase (HDAC) inhibition has been proposed for HB, we hypothesized that we could find an effective combination treatment strategy utilizing HDAC inhibition. METHODS: RNA sequencing, microarray, NanoString, and immunohistochemistry data of patient HB samples were analyzed for HDAC class expression. Patient-derived spheroids (PDSp) were used to screen combination chemotherapy with an HDAC inhibitor, panobinostat. Patient-derived xenograft (PDX) mouse models were developed and treated with the combination therapy that showed the highest efficacy in the PDSp drug screen. RESULTS: HDAC RNA and protein expression were elevated in HB tumors compared to normal livers. Panobinostat (IC50 of 0.013-0.059 µM) showed strong in vitro effects and was associated with lower cell viability than other HDAC inhibitors. PDSp demonstrated the highest level of cell death with combination treatment of vincristine/irinotecan/panobinostat (VIP). All four models responded to VIP therapy with a decrease in tumor size compared to placebo. After 6 weeks of treatment, two models demonstrated necrotic cell death, with lower Ki67 expression, decreased serum alpha fetoprotein and reduced tumor burden compared to paired VI- and placebo-treated groups. CONCLUSIONS: Utilizing a preclinical HB pipeline, we demonstrate that panobinostat in combination with VI chemotherapy can induce an effective tumor response in models developed from patients with high-risk, relapsed, and treatment-refractory HB. IMPACT AND IMPLICATIONS: Patients with treatment-refractory hepatoblastoma have limited treatment options with survival rates of less than 50%. Our manuscript demonstrates that combination therapy with vincristine, irinotecan, and panobinostat reduces the size of high-risk, relapsed, and treatment-refractory tumors. With this work we provide preclinical evidence to support utilizing this combination therapy as an arm in future clinical trials.

Ionogels for flexible conductive substrates and their application in biosensing.

Ionogels are highly conductive gels made from ionic liquids dispersed in a matrix made of organic or inorganic materials. Ionogels are known for high ionic conductivity, flexibility, high thermal and electrochemical stability. These characteristics make them suitable for sensing and biosensing applications. This review discusses about the two main constituents, ionic liquids and matrix, used to make ionogels and effect of these materials on the characteristics of ionogels. Here, the material properties like mechanical, electrochemical and stability are discussed for both polymer matrix and ionic liquid. We have briefly described about the fabrication methods like 3D printing, sol-gel, blade coating, spin coating, aerosol jet printing etc., used to make films or coating of these ionogels. The advantages and disadvantages of each method are also briefly summarized. Finally, the last section provides a few examples of application of flexible ionogels in areas like wearables, human-machine interface, electronic skin and detection of biological molecules.

Theranostic applications of peptide-based nanoformulations for growth factor defective cancers.

Growth factors play a pivotal role in orchestrating cellular growth and division by binding to specific cell surface receptors. Dysregulation of growth factor production or activity can contribute to the uncontrolled cell proliferation observed in cancer. Peptide-based nanoformulations (PNFs) have emerged as promising therapeutic strategies for growth factor-deficient cancers. PNFs offer multifaceted capabilities including targeted delivery, imaging modalities, combination therapies, resistance modulation, and personalized medicine approaches. Nevertheless, several challenges remain, including limited specificity, stability, pharmacokinetics, tissue penetration, toxicity, and immunogenicity. To address these challenges and optimize PNFs for clinical translation, in-depth investigations are warranted. Future research should focus on elucidating the intricate interplay between peptides and nanoparticles, developing robust spectroscopic and computational methodologies, and establishing a comprehensive understanding of the structure-activity relationship governing peptide-nanoparticle interactions. Bridging these knowledge gaps will propel the translation of peptide-nanoparticle therapies from bench to bedside. While a few peptide-nanoparticle drugs have obtained FDA approval for cancer treatment, the integration of nanostructured platforms with peptide-based medications holds tremendous potential to expedite the implementation of innovative anticancer interventions. Therefore, growth factor-deficient cancers present both challenges and opportunities for targeted therapeutic interventions, with peptide-based nanoformulations positioned as a promising avenue. Nonetheless, concerted research and development endeavors are essential to optimize the specificity, stability, and safety profiles of PNFs, thereby advancing the field of peptide-based nanotherapeutics in the realm of oncology research.

Gelatin-PVP dissolving microneedle-mediated therapy for controlled delivery of nifedipine for rapid antihypertension treatment.

Nifedipine has exhibited to be the oldest primary drug having promising therapeutic potential for hypertension, angina pectoris, and pre-eclampsia treatment which are the most emergency serious complications worldwide. Moreover, for long-term treatment transdermal route of delivery using polymeric dissolving microneedles (DMNs) patches has shown greater advantages, thus enhancing treatment compliance, painless, reducing the daily number of doses, prolonged release in a controlled manner, and variable bioavailability making this an ideal candidate for the transdermal therapeutic system. Here, we fabricated DMN patches made of gelatin and PVP using PDMS molds loaded with nifedipine drugs for a controlled painless delivery for a longer stable duration. The prepared gelatin-PVP (gel-PVP) DMN patches loaded with nifedipine were fabricated by centrifugation casting method. The characterization results displayed excellent mechanical strength of the needles to penetrate the skin. SEM and confocal microscopy showed penetration of the needles up to 567-600 µm using rhodamine B applied to the hairless punctured skin site. FTIR study exhibited no degradation of the drug was observed while fabricating the DMNs patch at different pH 7.4 and 4. Skin resealing test proved that there was immediate resealing of the skin observed within 10-15 min. Further in-vitro drug release profile study was carried out by dissolution method at different pH 7.4 and 4 showed sustained release of the drug up to 96 ± 2% till 48-72 h avoiding polymer or drug loss which was quantified by UV vis spectrophotometer at 235 nm absorbance showed stable release of the drug upto 48-72 h. A stability study carried out by the HPLC method showed the DMN patches loaded with the drug were found to be stable for up to 30 days at 25 °C. This novel preliminary data are the first study to our knowledge introducing these fabricated nifedipine gel-PVP DMN patches were found to be very efficient and showed prolonged controlled release up to 48-72 h thereby treating hypertension in a convenient, painless manner. This DMN patch-formulated design might act as a potential approach leading to a controllable, self-administrative, and rapid transdermal delivery system.

Influence of Defect Engineering in Nanocrystalline CeO2 for Therapeutics of Reactive Oxygen Species-mediated Disorders.

Intracellular oxidative stress generation is a root cause of the dysfunctioning of mitochondria that is accountable for neurodegenerative disorders. In nano-CeO2, the intrinsic redox cycle (Ce3+ ⇔ Ce4+) confers them with a distinct oxygen buffering ability. Thus, increasing the Ce3+/Ce4+ ratio by preferentially engineering oxygen vacancies is expected to boost the antioxidant characteristics in CeO2 nanocrystals (NCs) and hold promise in nanotherapeutics of neurodegenerative disorders. Here, a pristine, economic, and scalable synthesis route with rapid nucleation-growth to yield monodispersed CeO2 NCs of 4 nm has been employed. The NCs demonstrated sustained colloidal stability (zeta potential ~ -30.3±7.2 mV). The survival rate (~96.1% for 0.1 mg/mL) of healthy L929 cells and cell apoptosis induced on the SH-SY5Y cells (~ 30.2% for 0.1 mg/mL) indicate nano-CeO2s' prospects in nanomedicine. The formulated sustainable synthesis strategy for the enrichment of defects in these NCs is anticipated to pave the way for nanocrystal-based-treatments in smart healthcare.Clinical Relevance-This investigation signifies the oxygen vacancy-dependent therapeutic efficacy of CeO2 NCs by ensuring ~96.1% survival rate of L929 cells while demonstrating cell apoptosis on SH-SY5Y cells (~ 30.2%) to establish newer insights on treatment of neurodegenerative disorders.

Pathophysiology to advanced intra-articular drug delivery strategies: Unravelling rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most prevalent life-long autoimmune diseases with an unknown genesis. It primarily causes chronic inflammation, pain, and synovial joint-associated cartilage and bone degradation. Unfortunately, limited information is available regarding the etiology and pathogenesis of this chronic joint disorder. In the last few decades, an improved understanding of RA pathophysiology about key immune cells, antibodies, and cytokines has inspired the development of several anti-rheumatic drugs and biopharmaceuticals to act on RA-affected joints. However, life-long frequent systemic high doses of commercially available drugs are currently a limiting factor in the efficient management of RA. To address this issue, various single and double-barrier intra-articular drug delivery systems (IA-DDSs) such as nanocarriers, microparticles, hydrogels, and particles-hybrid hydrogel composite have been developed which can exclusively target the RA-affected joint cavity and release the precisely controlled therapeutic drug concentration for prolonged time whilst avoiding the systemic toxicity. This review provides a comprehensive overview of the pathogenesis of RA and discusses the rational design and development of biomaterials-based novel IA-DDs, ranging from conventional to advanced systems, for improved treatment of RA. Therefore, this review aims to unravel the pathophysiology of rheumatoid arthritis and explore cutting-edge IA-DD strategies exploiting biomaterials. It offers researchers a consolidated and up-to-date resource platform to analyze existing knowledge, identify research gaps, and contribute to the scientific literature.

Influence of PEGylation on WS2 Nanosheets and Its Application in Photothermal Therapy.

Photothermal therapy (PTT) is an alternative cancer therapy with minimal side effects and higher efficiency and selectivity. In this study, WS2 nanosheets were developed by ultrasonic exfoliation with different ratios of polyethylene glycol (PEG), and their effects on physicochemical properties were studied. The utilization of PEG during sonication significantly influenced the size and thickness of the resulting WS2 nanosheet layers, which was confirmed through scanning electron microscopy, atomic force microscopy, and dynamic light scattering analyses. PEG functionalization also improved the dispersibility of WS2 in aqueous solution by making its surface hydrophilic, which resulted in better biocompatibility. The intrinsic near-infrared absorbance of the nanosheets positions them as valuable agents for PTT. The study further explores the efficacy of these nanosheets as photothermal agents in the ablation of MDAMB-231 breast cancer cells. Although the use of PEG to demonstrate exfoliation and biocompatibility for WS2 has been reported previously, the effect of PEGylation on various physicochemical properties has not been studied in-depth until now. This study paves the way for the use of highly versatile PEG across a range of 2D material systems.

Synthesis and screening for anticancer activity of two novel telluro-amino acids: 1,3-Tellurazolidine-4-carboxylic acid and tellurohomocystine.

Tellurium (Te) containing amino acids and their derivatives have the potential to participate in biological processes, which are currently being studied extensively to understand the function of Te in biological and pharmacological activities. Here, we are reporting the synthesis of two novel Te-containing unnatural amino acids; 1,3-Tellurazolidine-4-carboxylic acid [Te{CH2CH(COOH)NHCH2}] 5, and 4,4'-(1,2-Ditellurdiyl)bis(2-aminobutanoic acid), i.e., tellurohomocystine [TeCH2CH2CH(NH2)COOH]2 7, synthesized from tellurocystine, and L-methionine as precursors, respectively. These telluro-amino acids were thoroughly characterized by multinuclear (1H, 13C, 125Te) NMR spectroscopy, high-resolution ESI-mass spectrometry (ESI-MS), and elemental analysis. The telluro-amino acids 5 and 7 demonstrated good biocompatibility when in vitro cytotoxicity was analyzed on two fibroblast cell lines L929 and NIH/3T3. The treatment of telluro-amino acids 1,3-Tellurazolidine-4-carboxylic acid 5 and tellurohomocystine 7 on breast cancer cell line MCF-7 showed anticancer activity with IC50 values of 7.29 ± 0.27 µg/mL and 25.36 ± 0.12 µg/mL, respectively. The cell cycle distribution studies also revealed arrest at the sub-G1 phase suggesting telluro-amino acids to be apoptotic.

Mechanistic insights on Bi-potentiodynamic control towards atomistic synthesis of electrocatalysts for hydrogen evolution reaction.

Herein, electrochemically assisted dissolution-deposition (EADD) is utilized over a three-electrode assembly to prepare an electrocatalyst for hydrogen evolution reaction (HER). Cyclic voltammetry is performed to yield atomistic loading of platinum (Pt) over SnS2 nanostructures via Pt dissolution from the counter electrode (CE). Astonishingly, the working electrode (WE) swept at 50 mV/s is found to compel Pt CE to experience 1000-3000 mV/s. The effect of different potential scan rates at the WE have provided insight into the change in Pt dissolution and its deposition behaviour over SnS2 in three electrode assembly. However, uncontrolled overpotentials at CE in a three-electrode assembly made Pt dissolution-deposition behavior complex. Here, for the first time, we have demonstrated bi-potentiodynamic control for dissolution deposition of Pt in four-electrode assembly over Nickel (Ni) foam. The dual cyclic voltammetry is applied to achieve better control and efficiency of the EADD process, engendering it as a pragmatically versatile and scalable synthesis technique.

A dipyridophenazine Ni(II) dithiolene complex as a dual-acting cancer phototherapy agent activatable within the phototherapeutic window.

A combination of photodynamic therapy (PDT) and photothermal therapy (PTT) within the phototherapeutic window (600-900 nm) can lead to significantly enhanced therapeutic outcomes, surpassing the efficacy observed with PDT or PTT alone in cancer phototherapy. Herein, we report a novel small-molecule mixed-ligand Ni(II)-dithiolene complex (Ni-TDD) with a dipyridophenazine ligand, demonstrating potent red-light PDT and significant near-infrared (NIR) light mild-temperature PTT activity against cancer cells and 3D multicellular tumour spheroids (MCTSs). The four-coordinate square planar complex exhibited a moderately intense absorption band (ε âˆ¼ 3700 M-1cm-1) centered around 900 nm and demonstrated excellent dark and photostability in an aqueous phase. Ni-TDD induced a potent red-light (600-720 nm) PDT effect on HeLa cancer cells (IC50 = 1.8 µM, photo irritation factor = 44), triggering apoptotic cell death through efficient singlet oxygen generation. Ni-TDD showed a significant intercalative binding affinity towards double-helical calf thymus DNA, resulting in a binding constant (Kb) âˆ¼ 106 M-1. The complex induced mild hyperthermia and exerted a significant mild-temperature PTT effect on MDA-MB-231 cancer cells upon irradiation with 808 nm NIR light. Simultaneous irradiation of Ni-TDD-treated HeLa MCTSs with red and NIR light led to a remarkable synergistic inhibition of growth, exceeding the effects of individual irradiation, through the generation of singlet oxygen and mild hyperthermia. Ni-TDD displayed minimal toxicity towards non-cancerous HPL1D and L929 cells, even at high micromolar concentrations. This is the first report of a Ni(II) complex demonstrating red-light PDT activity and the first example of a first-row transition metal complex exhibiting combined PDT and PTT effects within the clinically relevant phototherapeutic window. Our findings pave the way for designing and developing metal-dithiolene complexes as dual-acting cancer phototherapy agents using long wavelength light for treating solid tumors.

Role of Reassurance and Proper Mechanical Support Advice on Quality of Life and Pain Relief in Patients of the Mastalgia-A Prospective Follow-up Study at A Tertiary Care Center in a Developing Country.

Objective: To study the effect of reassurance and proper mechanical support on quality of life (QOL) and visual analogue score (VAS) pain assessment in patients with mastalgia at a range of follow-ups. Materials and Methods: A prospective follow-up study was conducted among women aged 15-45 years, complaining of breast pain without any abnormality detected clinically and radiologically. After consent to participate and enrollment, all the study participants were counseled and reassured about the non-neoplastic nature of the disease and about wearing proper mechanical support/Bra; this was repeated at each follow-up. VAS was used to assess the pain intensity perceived by the woman at each follow-up, post intervention. The Short Form-36 (SF-36) scale was used to evaluate health related QOL (HRQOL). Results: Among 80 patients, 31.2% were wearing a Bra of fabric other than cotton, 21.2% were wearing a loose fit mechanical support/Brassiere, while 10% were not wearing any mechanical support at baseline. The overall mean VAS score was significantly reduced with each follow-up, indicating decreased perception of breast pain over time. There was a significant difference between the mean SF-36 score between base line and after three months (p<0.0001). Mean scores in all domains of the SF-36 increased. The greatest reduction in mean VAS score was seen in 26-35 years age group and women with a body mass index <18.5 kg/m2. Conclusion: Reassurance and wearing proper mechanical support/Bra are effective for improving QOL and alleviating breast pain/mastalgia. These simple processes should be used for the management of mastalgia.

Posttranscriptional regulation of the prostaglandin E receptor spliced-isoform EP3-γ and its implication in pancreatic ß-cell failure.

In Type 2 diabetes (T2D), elevated lipid levels have been suggested to contribute to insulin resistance and ß-cell dysfunction. We previously reported that the expression of the PGE2 receptor EP3 is elevated in islets of T2D individuals and is preferentially stimulated by palmitate, leading to ß-cell failure. The mouse EP3 receptor generates three isoforms by alternative splicing which differ in their C-terminal domain and are referred to as mEP3α, mEP3ß, and mEP3γ. We bring evidence that the expression of the mEP3γ isoform is elevated in islets of diabetic db/db mice and is selectively upregulated by palmitate. Specific knockdown of the mEP3γ isoform restores the expression of ß-cell-specific genes and rescues MIN6 cells from palmitate-induced dysfunction and apoptosis. This study indicates that palmitate stimulates the expression of the mEP3γ by a posttranscriptional mechanism, compared to the other spliced isoforms, and that the de novo synthesized ceramide plays an important role in FFA-induced mEP3γ expression in ß-cells. Moreover, induced levels of mEP3γ mRNA by palmitate or ceramide depend on p38 MAPK activation. Our findings suggest that mEP3γ gene expression is regulated at the posttranscriptional level and defines the EP3 signaling axis as an important pathway mediating ß-cell-impaired function and demise.

Screening of AS101 analog, organotellurolate (IV) compound 2 for its in vitro biocompatibility, anticancer, and antibacterial activities.

Organotellurium compounds are being well researched as potential candidates for their functional roles in therapeutic and clinical biology. Here, we report the in vitro anticancer and antibacterial activities of an AS101 analog, cyclic zwitterionic organotellurolate (IV) compound 2 [Te-{CH2CH(NH3+)COO}(Cl)3]. Different concentrations of compound 2 were exposed to fibroblast L929 and breast cancer MCF-7 cell lines to study its effect on cell viability. The fibroblast cells with good viability confirmed the biocompatibility, and compound 2 also was less hemolytic on RBCs. A cytotoxic effect on MCF-7 breast cancer cell line investigated compound 2 to be anti-cancerous with IC50 value of 2.86 ± 0.02 µg/mL. The apoptosis was confirmed through the cell cycle phase arrest of the organotellurolate (IV) compound 2. Examination of the antibacterial potency compound 2 was done based on the agar disk diffusion, minimum inhibitory concentration, and time-dependent assay for the Gram-positive Bacillus subtilis and Gram-negative Pseudomonas putida. For both bacterial strains, tests were performed with the concentration range of 3.9-500 µg/mL, and the minimum inhibition concentration value was found to be 125 µg/mL. The time-dependent assay suggested the bactericidal activity of organotellurolate (IV) compound, 2 against the bacterial strains.