Antifibrotic Agent Mediated Tumor Microenvironment Modulation and Improved Nanomedicine Delivery in Solid Tumor.

The unique physiology of tumors limits the efficacy of chemotherapeutics. In efforts to improve the effectiveness of the existing chemotherapy drugs, nanomedicine emerged as a new hope but proved inadequate due to the transport barriers present within the tumor tissues, which limits the potential of nanomedicine. Dense collagen networks in fibrotic tissues contribute to hindering the penetration of molecular- or nano-scale medicine through tumor interstitium. In the present study, human serum albumin (HSA)-based nanoparticles (NPs) were developed for gemcitabine (GEM) and losartan (LST), which could offer secreted protein acids rich in cysteine (SPARC) and enhanced permeability and retention effect (EPR)-mediated drug accumulation in tumors. Also, the tumor microenvironment (TME) modulation approach using LST was coupled to investigate the impact on antitumor efficacy. GEM-HSA NPs and LST-HSA NPs were prepared by the desolvation-cross-linking method and characterized for size, potential, morphology, drug loading, drug-polymer interactions, and hemocompatibility. For investigating the efficacy of prepared NPs, cytotoxicity and mechanisms of cell death were elucidated in vitro by using various assays. Intracellular uptake studies of prepared HSA NPs indicated their uptake and cytoplasmic localization. Furthermore, in vivo studies demonstrated significantly improved anticancer efficacy of GEM-HSA NPs in combination with LST pretreatment. Extended LST treatment further improved the anticancer potential. It was shown that the improved efficacy of the nanomedicine was correlated with the reduced thrombospondin-1 (TSP-1) and collagen level in tumor tissue upon LST pretreatment. Moreover, this approach exhibited augmented nanomedicine accumulation in the tumor, and hematological, biochemical, and tissue histology indicated the safety profile of this combination regimen. Concisely, the undertaken study demonstrated the potential of the triple targeting (SPARC, EPR, TME modulation) approach for augmented efficacy of chemotherapeutics.

Codelivery of Gemcitabine and MUC1 Inhibitor Using PEG-PCL Nanoparticles for Breast Cancer Therapy.

In breast cancer therapy, Gemcitabine (Gem) is an antineoplastic antimetabolite with greater anticancer efficacy and tolerability. However, effectiveness of Gem is limited by its off-target effects. The synergistic potential of MUC1 (mucin 1) inhibitors and Gem-loaded polymeric nanoparticles (NPs) was discussed in this work in order to reduce dose-related toxicities and enhance the therapeutic efficacy. The double emulsion solvent evaporation method was used to prepare poly(ethylene glycol) methyl ether-block-poly-caprolactone (PEG-PCL)-loaded Gem and MUC 1 inhibitor NPs. The average size of Gem and MUC 1 inhibitor-loaded NPs was 128 nm, with a spherical shape. Twin-loaded NPs containing Gem and the MUC1 inhibitor decreased IC50 and behaved synergistically. Furthermore, in vitro mechanistic studies, that is, loss of MMP, clonogenic assay, Annexin V FITC assay, and Western blotting to confirm apoptosis with simultaneous induction of autophagy using acridine orange (AO) staining were performed in this study. Furthermore, the investigated NPs upon combination exhibited greater loss of MMP and decreased clonogenic potential with simultaneous induction of autophagy in MCF-7 cells. Annexin V FITC clearly showed the percentage of apoptosis while Western blotting protein expression analysis revealed an increase in caspase-3 activity with simultaneous decrease in Bcl-2 protein expression, a hallmark of apoptosis. The effectiveness of the Ehrlich ascites solid (EAT) mice treated with Gem-MUC1 inhibitor NPs was higher than that of the animals treated alone. Overall, the combined administration of Gem and MUC1 inhibitor-loaded NPs was found to be more efficacious than Gem and MUC1 inhibitor delivered separately.

Nisin and nisin-loaded nanoparticles: a cytotoxicity investigation.

OBJECTIVE: Nisin is an antibacterial peptide with anticancer properties, but the main drawback is its rapid enzymatic degradation and limited permeation across the cell membrane. This research aims to overcome these drawbacks by developing nisin-loaded nanoparticles (NPN) with improved cytotoxic effects. SIGNIFICANCE: PLGA nanoparticles are one of the most effective biodegradable and biocompatible drug delivery carriers. In the present study, nisin-loaded nanoparticles showed enhanced anticancer effects. METHODS: NPN was prepared by a double emulsion solvent evaporation method and characterized for different parameters. The cytotoxic investigation of NPN was carried out on various cell lines, including A549, SW-620, HT-29, PC-3, MDA-MB-231, MCF-7, MiaPaca-2, and fR2 by sulforhodamine B (SRB) assay. Mechanistic investigation of cellular cytotoxicity was performed by using bright-field microscopy, DAPI staining, intracellular reactive oxygen species (ROS), changes in mitochondrial membrane potential (ΔΨm), Western blotting and cellular uptake study. A comparative cytotoxicity study of nisin and NPN was performed on normal breast epithelial cells (fR2). RESULTS: NPN showed spherical shape, 289.09 ± 3.63 nm particle size, and 63.37 ± 3.12% entrapment efficiency. NPN was more cytotoxic to the MDA-MB-231 cell line, showing higher nuclear fragmentation, ROS generation, depletion of ΔΨm, and enhanced intracellular uptake with apoptosis signs compared with nisin and with no cytotoxicity on normal cells. CONCLUSIONS: The findings suggest that nisin delivery via PLGA nanoparticles can be used to treat cancer without significant effects on healthy cells.

Histopathological Differentiation of Antemortem and Postmortem Electrical Burn Mark Produced by Low Voltage.

ABSTRACT: The study was undertaken to differentiate antemortem electrical (AME) and postmortem electrical (PME) burn marks with the help of histopathology. The electrical burn mark was produced on 25 dead bodies. Alongside 25 cases of electrocution deaths were included for comparison. Slides were prepared and stained with hematoxylin-eosin stains. Intraepidermal and subepidermal separation; coagulative necrosis of the epidermis; nuclear elongation and hyperchromasia of epidermal cells; homogenization of the dermis; nuclear elongation and hyperchromasia of hair follicles, sweat glands, sebaceous glands, and blood vessel endothelium were studied for histopathological changes and graded. The findings of the study suggest that the histopathological changes in electrical burn marks are due to the physical effect of heat produced by the electric current. The classical histopathological features of electrical burn mark cannot differentiate between AME and PME burn marks. However, careful evaluation of grading of the dermal changes can be helpful in differentiating AME and PME burn marks. Highest grade of dermal thickness homogenization and highest grade of nuclear elongation of dermal appendages were significantly more in the antemortem electrical burn marks than PME burn marks.

An unusual patterned injury from homicidal craniocerebral impalement with a metal chair leg.

A 26-year-old young man died shortly after he had suffered craniocerebral impalement from a metal chair leg during an affray at an airport bar. At autopsy a 25 mm diameter circular wound was present in the left parietal region with protruding brain tissue. Death was due to craniocerebral trauma from a penetrating injury to the head. Examination of the chair used in the assault showed a metal chair with smeared blood on the front right leg that matched the blood group of the decedent. The fatal wound had been inflicted by the assailant with the victim leaning forward while kneeling on the floor. The assault had produced an unusual circular patterned defect in the left parietal bone with dimensions corresponding to the chair leg. The location of the defect and the use of a chair leg were two very unusual features in this homicide.

Association of menstruation cycle with completed suicide: a hospital-based case-control study.

The purpose of the study was to determine the phases of the menstrual cycle in the reproductive age group of females who committed suicide as compared with a control group of females who died from causes other than suicide. The study included 86 cases in the suicidal group and 80 cases in the non-suicidal group. The menstrual phase was decided by the gross and histological examination of the uterus and ovary at autopsy. Deaths were more common during the secretory phase (56.9%) in the suicidal group, while in the non-suicidal group, death occurred more commonly in the proliferative phase (66.3%). In reference to proliferative phase, deaths were more in the secretory phase and menstrual phase in the suicidal group, adjusted odd's ratio (OR) being 3.7 (p = 0.042) and 4.7 (p = 0.032), respectively. Corpus luteum was present in the right ovary of 43 and 14 victims of suicidal and non-suicidal deaths, respectively, while it was in the left ovary of 3 and 11 victims of suicidal and non-suicidal death, respectively. Odd's ratio was 10.3 for corpus luteum to be in the right ovary in comparison with the left ovary for the suicidal group (p = 0.001). This study revealed that suicidal chances in a woman are significantly more in the menstrual phase and the secretory phase of the menstrual cycle. The presence of corpus luteum in the right ovary is associated with an increased risk of suicide, but the reason is not known.

Body Coloration Artifacts Encountered at Medicolegal Autopsy in India.

Application of color on the external body surface before, during, and after death, such as during a festivity, cultural occasion, or after death ritual, can present as an artifact at forensic autopsy. The present study is a retrospective review of body color artifacts collected from postmortem reports, inquest papers and photographs of each individual case autopsied at our institutes during a 12 year period from 2004 to 2015. The reason for body colorations were various festivities, after death rituals and beautification products, among others. The body coloration mimicked antemortem changes, such as cyanosis, injury, jaundice, and congestion, as well as postmortem changes, such as postmortem lividity and early decomposition changes. These artifacts were differentiated by seeing the body before the washing of the color, history of the application of the color, and by various additional features, such as unusual appearance, distribution, and sites. They were not supported by any other findings on the body to consider them as genuine antemortem or postmortem findings.

Recent Advances in Formulation Strategies for Efficient Delivery of Vitamin D.

Deficiency of vitamin D is a global concern affecting a huge number of human populations. This deficiency has a serious impact on human health not only affecting bone mineral density but also becoming the reason for cardiovascular disorders, infectious diseases, autoimmune diseases and cancers. Exposure to sunlight is the major source of vitamin D, but due to the present day-to-day lifestyle of working in a shade arouses the need for exogenous sources of vitamin D. Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) are the two major forms of vitamin D, which are hydrophobic in nature and highly susceptible to environmental conditions, like temperature and light. Therefore, novel drug delivery systems could be explored for efficient delivery of vitamin D. In this review, a brief account of vitamin D is provided followed by a detailed description of recent advances in various delivery systems, including solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery systems, polymeric nanoparticles and solid dispersion, for the efficient delivery of vitamin D.

Mortality among homeless women who remain unclaimed after death: An insight.

BACKGROUND: Some homeless people remain unclaimed after death. Although women constitute a minor proportion among the homeless, they represent a more vulnerable section. We reviewed the major autopsy characteristics and causes of death among women whose bodies remained unclaimed after death. METHODS: We analysed the autopsy records and inquest papers of unclaimed bodies of women for the period 2006-12 at the Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, New Delhi. RESULTS: Most women whose bodies were unclaimed were 21 to 60 years old with a mean age of 45 years. Natural events (53.5%), largely attributable to acute/chronic lung diseases, were identified as the most common cause of death. Accidental deaths were predominant among the unnatural causes. Most bodies of women were found on the footpath besides the road (56.1%). CONCLUSION: The problems of physical/sexual abuse, acute chest infections and road traffic accidents are all aggravated in the situation of homelessness. More affordable shelters are needed to preferentially accommodate women. Also, awareness about the existing medical facilities needs to be increased.

Biodegradable nanocarrier of gemcitabine and tocopherol succinate synergistically ameliorates anti-proliferative response in MIA PaCa-2 cells.

Gemcitabine (GEM) is an important chemotherapeutic agent used alone or in combination with other anticancer agents for the treatment of various solid tumors. In this study, the potential of a dietary supplement, α-tocopherol succinate (TOS) was investigated in combination with GEM by utilizing human serum albumin-based nanoparticles (HSA NPs). The developed nanoparticles were characterized using DLS, SEM and FTIR and evaluated in a panel of cell lines to inspect cytotoxic efficacy. The ratio metric selected combination of the NPs was further investigated in human pancreatic cancer cell line (MIA PaCa-2 cells) to assess the cellular death mechanism via a myriad of biochemical and bio-analytical assays including nuclear morphometric analysis by DAPI staining, ROS generation, MMP loss, intracellular calcium release, in vitro clonogenic assay, cell migration assay, cell cycle analysis, immunocytochemical staining followed by western blotting, Annexin V-FITC and cellular uptake studies. The desolvation-crosslinking method was used to prepare the NPs. The average size of TOS-HSA NPs and GEM-HSA NPs was found to be 189.47 ± 5 nm and 143.42 ± 7.4 nm, respectively. In combination, the developed nanoparticles exhibited synergism by enhancing cytotoxicity in a fixed molar ratio. The selected combination also significantly triggered ROS generation and mitochondrial destabilization, alleviated cell migration potential and clonogenic cell survival in MIA PaCa-2 cells. Further, cell cycle analysis, Annexin-V FITC assay and caspase-3 activation, up regulation of Bax and down regulation of Bcl-2 protein confirmed the occurrence of apoptotic event coupled with the G0/G1 phase arrest. Nanocarriers based this combination also offered approximately 14-folds dose reduction of GEM. Overall, the combined administration of TOS-HSA NPs and GEM-HSA NPs showed synergistic cytotoxicity accompanied with dose reduction of the gemcitabine. These encouraging findings could have implication in designing micronutrient based-combination therapy with gemcitabine and demands further investigation.

PsychArray-Based Genome Wide Association Study of Suicidal Deaths in India.

Background: Suicide is a preventable but escalating global health crisis. Genome-wide association studies (GWAS) studies to date have been limited, and some are underpowered. In this study, we aimed to perform the PsychArray-based GWAS study to identify single nucleotide variations associated with suicide in the Indian population. Methods: We recruited unrelated subjects who died by suicide as cases (N = 313) and the non-suicidal deaths as controls (N = 294). The 607 samples were genotyped, including cases and controls using the Illumina Infinium PsychArray-24 BeadChip v1.3 Results: In our study, four single nucleotide polymorphisms (SNPs) crossed the threshold of significance level <1 × 10−5. One of them is intronic at Chromosome2:rs1901851 and three are intergenic at Chromosome12:rs3847911, Chromosome8:rs2941489, Chromosome8:rs1464092. At a significance level of 5 × 10−5, we found a few more SNPs, with the majority of them being intergenic variants. The associated genes were associated with various important functions ranging from cell signaling, GTP binding, GPCR binding, and transcription factor binding. Conclusions: The SNPs identified in our study were not reported earlier. To our best knowledge, this study is one of the first GWAS for suicide in the Indian population. The results indicate few novel SNPs that may be associated with suicide and require further investigation. Their clinical significance is to be studied in the future.

Redox-Responsive Hyaluronic Acid-Tacrolimus Conjugate: Synthesis, Characterization, and In Vitro Immunosuppressive Activity.

A redox-responsive macromolecular prodrug of tacrolimus, HA-ss-Tac, was constructed by conjugation of tacrolimus (TAC, FK506) through its succinate ester to cystamine-modified hyaluronic acid (HA-Cys), and its physicochemical properties and immunosuppressive activity were studied. The synthesized HA-ss-TAC was determined to contain 8% of chemically loaded TAC with significantly enhanced water solubility. The release study showed a sustained release of drug through slow degradation of linker-drug bonds. In vitro inhibition of proliferation of T- and B-lymphocytes was almost comparable to that of TAC, implying that the biologically active compound could be released from the conjugate. The polymeric prodrug lacks obvious cytotoxicity on Raw 264.7 macrophages and significantly suppressed the production of inflammatory cytokines IL-2 and IL-1ß by LPS-activated cells. Additionally, the cellular uptake study of the FITC-labeled conjugate confirmed the HA receptor-mediated internalization of the conjugate into targeted cells, thus avoiding systemic side effects. Taken together, the HA-ss-TAC prodrug could be an optimal prodrug for intravenous administration based on this preliminary data and can be expected to have improved therapeutic efficacy.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Suicidal deaths in pregnancy at an apex institute in India: A retrospective analysis of autopsy cases.

OBJECTIVE: Suicidal behavior in pregnancy is a known fact worldwide. However, the published literature is still debating whether pregnancy is associated with an increase in the risk of suicide. Nonetheless, this is an important phenomenon that should not be ignored as the life of an unborn fetus is involved. The present study is a retrospective analysis of suicide death in pregnancy for the years 2011-2020 to study the different parameters. METHODS: The cases were collected from the archives of the department with due permission from the authority. Data were analyzed according to the age of the victim, duration of pregnancy, and time and cause of death. RESULT: The commonest age group was 21-25 years, the time of death was mostly during the daytime, and most of the deaths were due to hanging. These findings are not unusual in comparison to the general population. The pregnancy duration of most of the cases was first and second trimester, and third-trimester pregnancy accounted for far less number. In contrast, some studies showed that suicidal ideation and depression were more common during the first trimester and third trimester. Most of the pregnant women were pregnant with male fetuses. CONCLUSION: Though suicidal ideation is more during the first and third trimester, suicide occurs mostly in the first and second trimester, with third-trimester suicide deaths being far less. Being pregnant with a male fetus might be a risk factor in comparison to having female fetuses. These are two aspects that need to be explored further.

Sudden death of an egg donor during oocyte retrieval due to ovarian hyperstimulation syndrome.

Ovarian Hyperstimulation Syndrome (OHSS) is uncommon among oocyte donors during in vitro fertilization (IVF) procedure and is rarely associated with death. We report a case of a 23-year-old oocyte donor who suddenly died on the operation table during oocyte retrieval. She had no risk factors in her menstrual history, laboratory, or clinical parameters. The antagonist cycle, triggered with the GnRH agonist protocol, was carried out. The cause of death at autopsy was attributed to respiratory failure due to acute massive pulmonary edema, which developed due to the complication of OHSS. Only a few autopsy cases associated with OHSS have been published, but, as far as we know, no clinical or autopsy cases of sudden death caused by OHSS have been reported.

Adverse Childhood Experiences, Aggression, Empathy, and Psychopathology in Adult Males Accused of Rape.

Background: Investigating the underlying psychosocial factors is a cornerstone of planning need-based intervention for adult males accused of rape. Unresolved debates on its etiology, mediation, or interaction among causal psychosocial variables fuel curiosity to scrutinize it further. Hence, we studied potential influence of and relation between adverse childhood experiences, aggression, empathy, and psychopathology in adult males accused of rape in India and investigated the risk factors for the same. Methods: With a correlational research design, 40 literate and consenting adult males medically confirmed for rape were recruited using convenient sampling. The assessment was done on Adverse Childhood Experiences, Aggression Questionnaire, Symptom Checklist-90, and Interpersonal Reactivity Index. Descriptive statistics, Pearson's product-moment correlation, and stepwise linear regression analysis were calculated. Results: Approximately 75% of the participants experienced at least one category of Adverse Childhood Experiences. Scores above cut-off points were obtained on anger, hostility, fantasy, and personal distress. Significant correlations were obtained between adverse childhood experiences and psychopathology; between hostility and psychopathology, perspective taking, and personal distress; and in case of indirect aggression, with perspective taking and empathetic concerns. Regression analysis revealed that an increase in Symptom Checklist-90 global scores increases hostility and that lower personal distress predicts higher scores on hostility on Aggression Questionnaire. Conclusions: Adverse childhood experiences, aggression, and psychopathology play a critical role and, therefore, should be included as core components of the prevention of rape or relapse prevention programs at the community level.

Implication of methylselenocysteine in combination chemotherapy with gemcitabine for improved anticancer efficacy.

The limitations associated with cancer monotherapy including dose dependent toxicity and drug resistance can be addressed by combination chemotherapy. The combination of antineoplastic agents improves the cytotoxic activity in comparison to the single-agent based therapy in a synergistic or an additive mode by reducing tumor growth as well as metastatic ability. In the present investigation, we explored the potential of methylselenocysteine (MSC) in combination chemotherapy with gemcitabine (GEM). The cytotoxic activity of GEM and MSC was determined in various cell lines and based on the activity, A549 cells were explored for the mechanistic studies including DAPI staining, measurement of oxidative stress, mitochondrial membrane potential loss, nitric oxide level, western blotting, cell migration and colony formation assays. A549 cells in combination treatment with MSC and GEM demonstrated enhanced cytotoxicity with more irregular cellular morphology as well as chromatin condensation and nuclear blebbing. The selected combination also significantly triggered ROS generation and mitochondrial destabilization, and alleviated cell migration potential and clonogenic propensity of A549 cells. Also, caspase-3 and PARP mediated apoptosis was observed in the combination treated cells. MSC based drug combination could offer the attributes of improved drug delivery and there was a 6-folds dose reduction of GEM in combination. Further, antitumor study in Ehrlich solid tumor model showed the efficacy of MSC combination with GEM for the enhanced antitumor activity. The proposed combination demonstrated the potential for further translational studies.

Mechanistic investigation of synergistic interaction of tocopherol succinate with a quinoline-based inhibitor of mammalian target of rapamycin.

OBJECTIVES: Cancer monotherapy is associated with various limitations; therefore, combination chemotherapy is widely explored for optimum drug efficacy. In this study, 4-(N-Phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl) quinoline-based mammalian target of rapamycin (mTOR) inhibitor (IIIM-4Q) was investigated in combination with tocopherol succinate (TOS), and the mechanism of cytotoxicity was elucidated. METHODS: The cytotoxic potential of IIIM-4Q and TOS was evaluated in five cell lines. Further, to understand the mechanism of cytotoxicity of IIIM-4Q, TOS and their combination, various studies including morphological analysis using scanning electron microscopy and 6-diamidino-2-phenylindole (DAPI) staining, estimation of reactive oxygen species (ROS) level, measurement of mitochondrial membrane potential (MMP), in-vitro cell migration assay, Western blotting and staining with acridine orange (AO) for autophagy detection were performed. KEY FINDINGS: Investigated combination was synergistic in nature and exhibited greater oxidative stress and mitochondrial dysfunction in pancreatic cancer cells. The migration potential of MIA PaCa-2 cells was significantly mitigated under the influence of this combination, and morphological changes such as chromatin condensation and nuclear blebbing were observed. Also, poly (adenosine diphosphate-ribose) polymerase cleavage and caspase-3 activation were observed in IIIM-4Q and TOS combination-treated cells. CONCLUSIONS: The investigated combination synergistically inhibited proliferation of MIA PaCa-2 cells through simultaneous induction of autophagy followed by apoptosis, and this combination demonstrated potential for further translational studies.

Chitosan-alginate nanoparticles of cabazitaxel: Design, dual-receptor targeting and efficacy in lung cancer model.

Cabazitaxel (CZT) loaded chitosan-alginate based (CSA) nanoparticles were developed with dual targeting functions of both folate receptor and epidermal growth factor receptor (EGFR) using ionic gelation technique. The chitosan-folate conjugate was synthesized, and characterized by using FTIR, NMR and Mass spectroscopy. The physicochemical parameters and morphology of all CSA nanoparticles were examined. The degree of conjugation of folic acid and cetuximab (CTXmab) was determined by UV-Visible spectroscopy and Bradford assay, respectively. Moreover, XPS analysis also supported the presence of the ligands on nanoparticles. The cellular-uptake study performed on A-549 cells demonstrated a significant enhancement in the uptake of dual-receptor targeted CSA nanoparticles than non-targeted and single-receptor targeted CSA nanoparticles. Further, CZT-loaded dual receptors targeted CSA nanoparticles also showed significantly lower IC50 values (~38 folds) than the CZT control against A-549 cells. Further, in-vivo histopathological evaluations of dual receptor-targeted CSA nanoparticles have demonstrated better safety in Wistar rats. Moreover, its treatment on the Benzo(a)pyrene (B(a)P) induced lung cancer mice model has showed the enhanced anticancer efficacy of CZT with a prolonged survival rate.

Development of the first DNA database and identification portal for identification of Unidentified bodies in India - UMID.

Identifying missing persons and unidentified dead bodies is a well-documented global problem in recent years. To curb this issue, countries such as the USA, UK, and Australia already have well-established DNA databases. Considering the alarming number of unidentified/unclaimed dead bodies reported in India every year, it is evident that the current practices are not sufficient to establish their identities. Forensic medicine professionals are ethically, morally, and dutybound to collect information about missing and unidentified persons and work with the government agencies to determine their identity. Concerning the social and public interest, we have developed the first-ever identification portal and DNA database of unidentified dead bodies autopsied at the Department of Forensic Medicine and Toxicology, AIIMS, New Delhi, India. After the investigation officer's informed consent, biological samples from unidentified dead bodies and a detailed phenotypic description, anthropological data and other visual characteristics of the deceased are recorded at the time of autopsy. This information is uploaded on our database which is available for public access, and the genotypic information generated through STR analysis is only available for internal usage.Claimants (biological relatives) may browse through the URL (https://umid-aiims.icmr.org.in/), and if they wish to claim an unidentified dead body, they may approach as per the given guidelines. The DNA profiles generated include a total of 16 STRs (15 autosomal tetranucleotide microsatellite STRs and 1 Sex Chromosome Specific STR). The claimant's STR profile is run through the questioned database to look for a potential match. If positive, the investigating officer of that particular case is informed for further necessary action. Until December 2020, our database consisted the information of 255 individuals and two unidentified cadavers were identified. This project's success can also lead to a pioneering National DNA database of unidentified and missing persons in India.