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.

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.

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.

A systematic review of the quality of abstracts reporting on randomized controlled trials presented at major international cardiothoracic conferences.

Conference proceedings are widely available and may represent the only report of given research. Poor reporting of randomized controlled trials (RCTs) in conference abstracts may impede interpretability. In 2008, the Consolidating Standards of Reporting Trials group published minimum standards for RCT reporting in conference abstracts (CONSORT-A). We sought to evaluate the reporting quality of abstracts presented at major international cardiothoracic conferences. Abstracts were retrieved for the annual meetings of 5 cardiothoracic societies over 3 consecutive years (2016 to 2018). After screening, those reporting on RCTs were scored by 2 independent reviewers against the 17-item CONSORT-A checklist. The primary endpoint was the total number of checklist criteria reported in individual abstracts. Statistical analysis was performed using STATA ICv16. Of 3233 screened abstracts, 100 (3.1%) reported on RCTs. Average checklist adherence was 35% (median 6/17 items, IQR 2-15) across abstracts. Author contact (n = 0), funding disclosures (n = 3, 2.9%) and randomization methodology (n = 5, 4.8%) were the least-frequently reported. There was no statistically-significant difference in terms of reporting quality between conferences (n = 0.07) or years (p = .06). Trial registration, word count (>300), multicentre trial design and mention of CONSORT in the abstract were associated with higher reporting quality. Reporting quality was not associated with successful full-length publication within 2 years (p = .33). The reporting quality of abstracts of RCTs presented at international cardiothoracic conferences is poor when benchmarked against the CONSORT-A standards. This highlights an area for targeted improvement.

Designing nanoformulation for the nose-to-brain delivery in Parkinson's disease: Advancements and barrier.

Parkinson's disease (PD), a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, which results in the loss of motor activity. In the management of PD, the primary aim is to increase the dopamine content in the brain either by delivering the precursors of dopamine or by inhibiting the molecules responsible for dopamine degradation. Due to the low bioavailability, a higher dosage of drugs needs to be administered repeatedly for achieving the desired therapeutic effect. This repeated high dose not only increases the severe side effects but also produces tolerance in the body. Often, direct administration of drugs fails to ameliorate the symptoms as the unmodified drugs cannot cross the blood-brain barrier (BBB). Nanotherapeutic is at the forefront of the alternative treatment against the central nervous system (CNS) disorders due to the ability to circumvents the BBB. Here, all the available treatments for PD have been discussed with their limitation. The current trends of nanotherapeutics for PD have been explored. Suitability and formulation prospects for nasal delivery have been analyzed in detail to explore new research scope. The most effective approach is the nose-to-brain delivery for targeting drugs directly to the brain. This delivery bypasses the BBB and concentrates more drugs at the target site. Thus, developments of nose-to-brain delivery of nanoformulations explicit the new scope to manage PD better. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Nanohybrids as Protein-Polymer Conjugate Multimodal Therapeutics.

Protein therapeutic formulations are being widely explored as multifunctional nanotherapeutics. Challenges in ensuring susceptibility and efficacy of nanoformulation still prevail owing to various interactions with biological fluids before reaching the target site. Smart polymers with the capability of masking drugs, ease of chemical modification, and multi-stimuli responsiveness can assist controlled delivery. An active moiety like therapeutic protein has started to be known as an important biological formulation with a diverse medicinal prospect. The delivery of proteins and peptides with high target specificity has however been tedious, due to their tendency to aggregate formation in different environmental conditions. Proteins due to high chemical reactivity and poor bioavailability are being researched widely in the field of nanomedicine. Clinically, multiple nano-based formulations have been explored for delivering protein with different carrier systems. A biocompatible and non-toxic polymer-based delivery system serves to tailor the polymer or drug better. Polymers not only aid delivery to the target site but are also responsible for proper stearic orientation of proteins thus protecting them from internal hindrances. Polymers have been shown to conjugate with proteins through covalent linkage rendering stability and enhancing therapeutic efficacy prominently when dealing with the systemic route. Here, we present the recent developments in polymer-protein/drug-linked systems. We aim to address questions by assessing the properties of the conjugate system and optimized delivery approaches. Since thorough characterization is the key aspect for technology to enter into the market, correlating laboratory research with commercially available formulations will also be presented in this review. By examining characteristics including morphology, surface properties, and functionalization, we will expand different hybrid applications from a biomaterial stance applied in in vivo complex biological conditions. Further, we explore understanding related to design criteria and strategies for polymer-protein smart nanomedicines with their potential prophylactic theranostic applications. Overall, we intend to highlight protein-drug delivery through multifunctional smart polymers.

Designing and Immunomodulating Multiresponsive Nanomaterial for Cancer Theranostics.

Cancer has been widely investigated yet limited in its manifestation. Cancer treatment holds innovative and futuristic strategies considering high disease heterogeneity. Chemotherapy, radiotherapy and surgery are the most explored pillars; however optimal therapeutic window and patient compliance recruit constraints. Recently evolved immunotherapy demonstrates a vital role of the host immune system to prevent metastasis recurrence, still undesirable clinical response and autoimmune adverse effects remain unresolved. Overcoming these challenges, tunable biomaterials could effectively control the co-delivery of anticancer drugs and immunomodulators. Current status demands a potentially new approach for minimally invasive, synergistic, and combinatorial nano-biomaterial assisted targeted immune-based treatment including therapeutics, diagnosis and imaging. This review discusses the latest findings of engineering biomaterial with immunomodulating properties and implementing novel developments in designing versatile nanosystems for cancer theranostics. We explore the functionalization of nanoparticle for delivering antitumor therapeutic and diagnostic agents promoting immune response. Through understanding the efficacy of delivery system, we have enlightened the applicability of nanomaterials as immunomodulatory nanomedicine further advancing to preclinical and clinical trials. Future and present ongoing improvements in engineering biomaterial could result in generating better insight to deal with cancer through easily accessible immunological interventions.

Addressing Maternal Mortality in Selected Districts of Madhya Pradesh, India - A Human Rights-based Approach.

BACKGROUND: Maternal mortality is an indicator of state of maternal health services, status of women, women's health, and above all developments of nation. OBJECTIVES: The objectives of the study were to identify the patterns and causes, medical as well as sociocultural, of maternal death as well as consider and list out the rights realization perspective of the mothers, their immediate families and the community at large. MATERIALS AND METHODS: A cross-sectional study was conducted in three districts of Madhya Pradesh, India, for 1 year. One hundred and two maternal deaths were covered, and verbal autopsy was conducted. Human right perspective was assessed using questionnaire. RESULTS: Majority (64.7%) of maternal deaths occurred between 18 and 25 years of age. About 50.9% were primigravida, and postpartum hemorrhage was the most common cause. Nearly 53.9% had visited more than one facility before death. CONCLUSION: Poor antenatal care and lack of human resources posed major reasons for death in all facilities. Rights realization among the beneficiaries was found to be very poor.