Diabetology and Nanotechnology: A Compelling Combination.

The convergence of diabetology and nanotechnology has emerged as a promising synergy with the potential to revolutionize the management and treatment of diabetes mellitus. Diabetes, a complex metabolic disorder affecting millions worldwide, necessitates innovative approaches to enhance monitoring, diagnosis, and therapeutic interventions. Nanotechnology, a burgeoning field that manipulates materials at the nanoscale, offers unprecedented opportunities to address the challenges posed by diabetes. This abstract explores the multifaceted interface between diabetology and nanotechnology, highlighting key areas of integration. Nanotechnology has paved the way for the development of advanced glucose monitoring systems with enhanced accuracy, sensitivity, and patient convenience. Miniaturized biosensors and implantable devices equipped with nanoscale materials enable continuous and real-time glucose monitoring, empowering individuals with diabetes to make timely and informed decisions about their dietary and insulin management. Furthermore, nanotechnology has facilitated breakthroughs in targeted drug delivery, addressing the limitations of conventional therapies in diabetes treatment. Nano-sized drug carriers can improve bioavailability, enable controlled release, and enhance the selectivity of therapeutic agents, minimizing side effects and optimizing treatment outcomes. Moreover, nanoengineered materials have opened avenues for tissue engineering and regenerative medicine, offering the potential to restore damaged pancreatic islets and insulin-producing cells. The amalgamation of diabetology and nanotechnology also holds promise for early disease detection and prevention. Nanoscale diagnostic tools, such as biomarker-based nanoprobes and lab-onchip devices, offer rapid and accurate detection of diabetes-related biomolecules, enabling timely interventions and reducing the risk of complications. However, this compelling combination also presents challenges that warrant careful consideration. Safety, biocompatibility, regulatory approval, and ethical implications are crucial factors that demand meticulous evaluation during the translation of nanotechnology-based solutions into clinical practice. In conclusion, the integration of diabetology and nanotechnology represents a transformative paradigm that has the potential to reshape the landscape of diabetes management. By harnessing the unique properties of nanoscale materials, researchers and clinicians are poised to usher in an era of personalized and precise diagnostics, therapeutics, and preventive strategies for diabetes mellitus. As advancements in nanotechnology continue to unfold, the journey towards realizing the full potential of this compelling combination remains an exciting frontier in medical science.

The Emergence of Nanotechnology in the Prognosis and Treatment of Myocardial Infarctions.

Myocardial infarction (MI), commonly known as a heart attack, is a critical cardiovascular condition associated with high morbidity and mortality rates worldwide. Despite significant advancements in traditional treatment modalities, there remains a need for innovative approaches to improve the prognosis and treatment outcomes of MI. The emergence of nanotechnology has provided a promising avenue for revolutionizing the management of this life-threatening condition. This manuscript aims to explore the role of nanotechnology in the prognosis and treatment of myocardial infarctions. Nanotechnology offers unique advantages in the field of cardiovascular medicine, including targeted drug delivery, precise imaging and diagnosis, regenerative medicine approaches, biosensors and monitoring, and the integration of therapy and diagnostics (theragnostic). One of the key advantages of nanotechnology is the ability to deliver therapeutic agents directly to the affected site. Nanoparticles can be engineered to carry drugs specifically to damaged heart tissue, enhancing their efficacy while minimizing off-target effects. Additionally, nanoparticles can serve as contrast agents, facilitating high-resolution imaging and accurate diagnosis of infarcted heart tissue. Furthermore, nanotechnology-based regenerative approaches show promise in promoting tissue healing and regeneration after MI. Nanomaterials can provide scaffolding structures or release growth factors to stimulate the growth of new blood vessels and support tissue repair. This regenerative potential holds significant implications for restoring cardiac function and minimizing long-term complications. Nanotechnology also enables real-time monitoring of critical parameters within the heart, such as oxygen levels, pH, and electrical activity, through the utilization of nanoscale devices and sensors. This capability allows for the early detection of complications and facilitates timely interventions. Moreover, the integration of therapy and diagnostics through nanotechnology-based platforms, known as theragnostic, holds tremendous potential. Nanoparticles can simultaneously deliver therapeutic agents while providing imaging capabilities, enabling personalized treatment strategies tailored to individual patients. This manuscript will review the recent advancements, clinical trials, and patents in nanotechnology for the prognosis and treatment of myocardial infarctions. By leveraging nanotechnology's unique properties and applications, researchers and clinicians can develop innovative therapeutic approaches that enhance patient outcomes, improve prognosis, and ultimately revolutionize the management of myocardial infarctions.

Genetic Diversity of Autosomal STR Markers in the Brahmin Population of Rajasthan and Haryana: Significance in Population and Forensic Genetics.

The aim of the study is to evaluate the suitability of STRs for molecular characterization and forensic applications in unrelated Brahmins of Rajasthan and Haryana states, India. Materials and Methods: A total of 203 male DNA samples from various districts of Haryana (n=104) and Rajasthan (n=99) were genotyped using the GlobalFiler® PCR Amplification Kit. Allelic frequencies and different forensic parameters like PD, PE, PIC, PM, Ho, He, UHe, and TPI were calculated with different software. Results: More than 200 alleles were present in both populations, ranging from 6.0 to 35.2 and SE33 was the most polymorphic marker. The combined power of discrimination was 1. To know the relatedness with other Indian Brahmin populations, the UPGMA dendrogram and principal component analysis plot were visualized to show that both populations are close to each other and in nearby Saraswat Brahmins of Himachal Pradesh. This study showed a genetic relationship and forensic examination in the Haryana and Rajasthan Brahmin populations and various ethno-linguistically diverse populations of India. Conclusion: The results imply that the highly polymorphic 21 autosomal STR loci might be applied for individuals' forensic identification and parentage testing. This study also suggests that the kit having both autosomal and Y-STR markers is appropriate for a better understanding of the genetic and forensic examination in the Brahmin population of Haryana and Rajasthan.

Nanocrystals: A Deep Insight into Formulation Aspects, Stabilization Strategies, and Biomedical Applications.

BACKGROUND: Drugs with poor solubility exhibit hurdles in their formulation due to poor dissolution and low bioavailability. Nanocrystallization is a great technique for incorporating poorly soluble drugs and is associated with many benefits. OBJECTIVE: The objective of the present review is to discuss formulation techniques for the generation of Nanocrystals (NCs) and illustrate the various advantages of NCs. It also explains commonly used stabilizers and guidelines for their safe use for enhancing NCs and provides a deep insight into various biomedical applications of NCs. METHODS: The review was extracted from the study carried out in the general literature to emphasize the importance of NCs in various formulations. RESULTS: NCs are a widely accepted approach to enhancing drug solubility. There are so many marketed products of nanocrystal drug formulations that are being used to treat life-threatening disorders. Two techniques can be used to formulate NCs, i.e., the bottom-up method and the top-down method. Their main biomedical applications are found in oral, parenteral, pulmonary, ocular, dermal, and mucosal formulations. CONCLUSION: In the present review, different formulation methods of NCs have been discussed in detail, followed by explaining the advantages and various targeted drug delivery systems covered by NCs formulations. The development of NCs-based formulation avoids the limitations of other systems used for targeted drug delivery.

Evaluation of genetic polymorphisms at 21 autosomal STR loci in Ramgharia Sikh population of Punjab, India.

BACKGROUND: STR (Short Tandem Repeat) markers are highly polymorphic markers, which are widely used in forensics DNA analysis and aid to ascertain unique genotype profiles of individuals and determine the genetic diversity of the given population. AIM: In the present study, an attempt has been made to evaluate the population genetic diversity of the Ramgharia Sikh population of Punjab, India, using 21 autosomal STR loci (D3S1358, vWA, D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, D2S441, D19S433, TH01, FGA, D22S1045, D5S818, D13S317, D7S820, SE33, D10S1248, D1S1656, D12S391, and D2S1338) to augment the emerging forensic database related to the indigenous population of India. SUBJECTS AND METHODS: For generation of the database, 200 (blood on FTA card) samples were obtained from genetically unrelated Ramgharia Sikhs residing in the state of Punjab. Twenty-one autosomal STR markers were analysed using the Globalfiler® PCR amplification kit. RESULTS: With the help of various statistical tools, a total of 232 alleles were observed and 11.048 ± 1.284 (mean ± standard deviation) alleles per locus were recorded. No locus deviated from Hardy Weinberg Equilibrium. SE33 locus was found to be the most polymorphic and exhibited the highest discrimination power, that is, 0.99. Moreover, results further indicated that Ramgharia Sikhs of Punjab showed a high affinity with Bhils of Madhya Pradesh (India). Thus, the studied population showed genetic proximity with the geographically close populations of India and showed significant genetic variations with distant populations, which was evident from the UPGMA tree and Principal Component Analysis plot. CONCLUSION: Overall, the 21 autosomal STRs were found to be polymorphic in the Ramgharia population and suitable for forensic casework and studies on population genetics.

Y-23 mediated genetic data analysis of endogamous Brahmin population of Rajasthan, India.

India's largest state Rajasthan is known for its variable population groups including castes, communities and tribes. In the present article, Y-STR polymorphisms of hundred unrelated healthy male volunteers from the Brahmin population of Rajasthan, India were investigated using the Powerplex® Y-23 PCR amplification kit. Total 94 distinct haplotypes were obtained out of them 93 were singletons. Haplotype Diversity (HD) and Discrimination Capacity (DC) for the population were 0.644 and 0.9894 respectively. The Intra-population relationship between the present population data and other reported Indian populations was examined through Multidimensional Scaling (MDS) Plot, which shows the Brahmin population of Rajasthan lies in a cluster with the Brahmin populations of Haryana and Maharashtra. Data generated with 23 Y-STR markers is submitted on Y chromosome haplotype reference database (YHRD) (yhrd.org) and it will robust the forensic database of the Rajasthan population of India.

Effect of postmortem interval and conditions of teeth on STR based DNA profiling from unidentified dead bodies.

Teeth are important exhibits to establish the identity of unidentified dead bodies by DNA profiling. Tooth acts as a cage to protect DNA from harsh environmental conditions. Unidentified bodies are sometimes found many years after death causing loss of valuable soft tissues which can be used for DNA extraction. Skeletal remains and dental evidence provide the best alternative when decomposed or burnt bodies are examined to establish the identity. In this study, the powder-free method was used to extract DNA from ninety-five teeth of unidentified dead bodies across seven years (2014-2020). Intact and broken dental remains were analyzed majorly from decomposed remains. The present study reports successful STR profiles obtained from dental evidence using powder free method. Complete DNA profiles were obtained from intact teeth while damaged teeth either gave partial profiles or no results. This data suggest that intact teeth are excellent samples for DNA profiling from decomposed unidentified dead bodies even with greater post mortem interval. Findings from this study can hence be useful in establishing the identity in forensic and archeological casework.

Key genetic and forensic attributes of Uttarakhand population of India.

The present study aimed to investigate the genetic and forensic attributes of Uttarakhand population based on 20 autosomal STR loci implemented in PowerPlex® 21 System. Results unveiled 219 alleles ranging from 6 (TH01, TPOX) to 20 (Penta E). Forensic analysis revealed locus Penta E as the most polymorphic and discriminative loci, whereas genetic analysis indicated presence of higher heterozygosity within population. Phylogenetic analysis indicated higher genetic affinity of Uttarakhand population with the neighbouring Himachal Pradesh population. Overall, the study indicates that the PowerPlex® 21 System is suitable for genetic and forensic analysis in Uttarakhand population.

Genetic evidence of shared ancestry among diverse ethno-linguistic human populations of Himachal Pradesh.

In Indian montane system, human populations often exhibit an unparallel social organization where inter-caste marriages are still not common. This attribute affects the demography and population genetic structure of the resident populations. Further, human populations residing in the mountains in India are poorly studied for their genetic make-up and allele distribution patterns. In the present study, we genotyped 594 unrelated individuals using PowerPlex® 21 System (Promega, USA) from eight different populations belonging to 12 districts of Himachal Pradesh which differed in ethnicity, language, geography and social organization. Altogether, we obtained 1415 alleles with a mean of 8.84 ± 0.26 alleles per locus and 0.80 mean observed heterozygosity. Locus Penta E showed the highest combined power of discrimination and was found most informative for forensic purposes. Interestingly, phylogenetic analysis grouped the populations of Rajputs, Scheduled castes and Brahmins into one cluster, which indicated a deep genetic admixture in the ancestral populations. This study documents the first-ever report on the population genetic assignment of various castes in Himachal Pradesh and unveils the facts of cryptic gene flow among the diverse castes in the northern hilly state of India. Our results showed a genetic relationship among the various ethno-linguistically diverse populations of India.

A Study on Knowledge and Awareness of Cervical Cancer Among Females of Rural and Urban Areas of Haryana, North India.

Lack of awareness of screening methods, risk factors, and symptoms may lead to late diagnosis and poor prognosis of cervical cancer. The plan of this study was to assess the level of awareness about cervical cancer and HPV vaccine among females of rural and urban areas of Haryana, India. This cross-sectional study was performed using a comprehensive self-designed questionnaire on 1500 women of urban (700) and rural (800) background aged 18-65 years, evaluating their knowledge for cervical cancer and screening, HPV infection and its preventive measure, and symptoms and risk factors. Data obtained was analyzed and interpreted by using simple percentages and bar charts. Most of the participants were aged between 21 and 30 years and had college level education. Majority of the women from rural areas had poor knowledge about cervical cancer (55%) and its screening (75%), HPV infection (87.5%), and HPV vaccine (95%) compared with urban areas. Knowledge about symptoms and risk factors was very low in both rural and urban areas. Whatever little knowledge the women had about cervical cancer was from college education, friends, neighbors, relatives, and medical practitioner or doctors. The survey pointed to the critical need to educate women about cervical cancer and its early diagnosis, related risk factors, symptoms, and preventive measures which can be achieved by launching extensive awareness programs for educating females about cervical cancer in India.

High-risk HPV infection modulates the promoter hypermethylation of APC, SFRP1, and PTEN in cervical cancer patients of North India.

Persistent infection with oncogenic HPV and downregulation of tumor suppressor genes play an essential role in the development and progression of cervical cancer. The present study aimed to identify the promoter methylation status of APC, SFRP1, and PTEN which are important regulators of Wnt pathway and their association with high-risk HPV infection and gene expression. Methylation Specific PCR (MSP) and quantitative reverse transcription PCR (RT-qPCR) were used to detect methylation status and gene expression levels of APC, SFRP1, and PTEN in cervical cancer biopsies (110) and paired non-cancerous biopsies (28). APC promoter was methylated in 38%, SFRP1 in 95%, and PTEN in 55% of the cervical cancer biopsies. Our data showed a trend of a higher rate of methylation of the gene promoters in cervical cancer biopsies while; they were majorly un-methylated in non-cancerous biopsies. Corresponding to a higher rate of methylation in cancer biopsies, the gene expression levels of APC, SFRP1, and PTEN were reduced in cervical cancer samples in comparison to normal cervix tissues. Further, we observed that 97% cancer biopsies were HPV infected and high-risk type HPV16 and 18 infections were significantly positively associated with APC (p = 0.008 and p = 0.007), SFRP1 (p = 0.003 and p = 0.0067), and PTEN (p = 0.049 and p = 0.008) promoter methylation. APC, SFRP1, and PTEN promoter hyper-methylation is positively associated with high-risk HPV infection and inversely associated with gene expression. Our findings show that high-risk HPV infection promotes methylation of these genes and further promotes their silencing.

Aberrant promoter methylation of NOTCH1 and NOTCH3 and its association with cervical cancer risk factors in North Indian population.

Cervical cancer is the fourth most common type of cancer in women worldwide, and associated mortality is highest in developing countries like India. Limited studies are available on the role of NOTCH signaling pathway and promoter methylation in cervical cancer. In the current study, we investigated the promoter methylation status of NOTCH receptor genes (mainly NOTCH1, NOTCH2, and NOTCH3) and its correlation with gene expression, clinicopathological factors, and prognosis of cervical cancer. A total cohort of 110 cervical cancer patients of North Indian origin was enrolled in the study. From 28 of these patients, biopsies from adjacent non-cancerous tissue were available to serve as healthy controls. Promoter methylation status and mRNA expression level of NOTCH1, NOTCH2, and NOTCH3 were determined by methylation-specific PCR (MSP) and real-time quantitative (RT-qPCR), respectively. NOTCH1 and NOTCH3 promoters were methylated in 92% (P<0.0001), and 61% (P<0.001) of the cervical cancer biopsies. We did not observe a statistically significant change in the promoter methylation level of NOTCH2. Further, NOTCH1, NOTCH2, and NOTCH3 were down-regulated in cervical cancer biopsies, but the differential expression of only NOTCH1 was found statistically significant. The promoter methylation levels of all three genes also showed a statistically significant association with clinicopathological factors and HPV infection (Type 16 and 18) but we did not observe a statistically significant relationship between their methylation status and gene expression. Overall our results provide evidence of the altered methylation and expression status of NOTCH1 and NOTCH3 receptor genes in cervical cancer. This study of NOTCH gene promoter methylation may provide a new perspective for early screening and diagnosis of cervical cancer.

Filgrastim loading in PLGA and SLN nanoparticulate system: a bioinformatics approach.

OBJECTIVE: In this research work, we hypothesized to predict the nanoparticulate system, best suited for targeted delivery of filgrastim. Significance: Targeted delivery of filgrastim to bone marrow is required to decrease the incidence of neutropenia/febrile neutropenia. This is achieved by nanoparticulate systems, duly designed by bioinformatics approach. METHOD: The targeted delivery of filgrastim in nanoparticulate system was achieved by molecular dynamics (MD) simulation studies. Two matrices comprising PLGA and SLN (tripalmitin, core component of SLN system) were modeled separately with proposed drug filgrastim. Energy minimization of all systems was done using the steepest descent method. PLGA and tripalmitin systems were equalized at 310 °C, at 1 bar pressure with Berendsen barostat for 200 ps using a v-rescale thermostat for 100 ps. Atomistic MD simulations of four model system and mass density of interacting systems were calculated. RESULTS: The mass density maps of each nanoparticle system, that is, PLGA and tripalmitin showed an increase in density toward the end of the simulation. The contact numbers attained equilibria with the average number of approx.. 1500 contacts in case of tripalmitin-filgrastim system. While PLGA-filgrastim system shows lesser contacts as compared to tripalmitin with average contacts of approx. 1000.The binding free energy was predicted to be -1104 kJ/mol in tripalmitin-filgrastim complex and -421 kJ/mol in PLGA-filgrastim system. CONCLUSION: Findings of study revealed that both nanoparticle systems assumed to be good model for drug-carrier systems. Though SLN systems were thought to be more appropriate than PLGA, still the in vivo findings could ascertain this hypothesis in futuristic work.

Evaluation of genetic polymorphism at 20 autosomal STR loci in Rajput population of Himachal Pradesh, India.

In the present study, genetic diversity indices and forensic parameters of Rajput population of Himachal Pradesh, India, were obtained at 20 autosomal short tandem repeat (STR) loci included in the PowerPlex® 21 System (Promega, USA). With 227 alleles and 11.35 ± 0.89 alleles per locus, none of the locus deviated from the Hardy-Weinberg equilibrium (HWE). The most polymorphic and discriminative locus was Penta E. Phylogenetic tree showed high genetic affinity of Rajput population of Himachal Pradesh with Rajputs of Madhya Pradesh and Yadav of Bihar. Overall, the tested 20 autosomal STRs were polymorphic in Rajput population and found suitable in forensic casework and population genetic studies.

Pomegranate supplementation attenuates inflammation, joint dysfunction via inhibition of NF-κB signaling pathway in experimental models of rheumatoid arthritis.

Incisive search of innovative compounds for regulating pain, inflammation, and bone damage, with nominal side effects has focused on nutritional supplements. The endeavor of this research work was to investigate, for first time, the inhibitory effect of pomegranate rind extract in established models of nociception and inflammation. Pomegranate (50, 100, and 200 mg/kg) and indomethacin (3 mg/kg) was assessed in eddy's hot plate-induced algesia, carrageenan, and Complete Freund's adjuvant-induced models in Wistar rats. Results of study conclude that pomegranate at a dose of 200 mg/kg showed significant (p < 0.001) reduction in paw swelling in both inflammatory experimental models. In addition, observations recorded a significant (p < 0.05) increase in nociceptive threshold. Henceforth, we might say that pomegranate (200 mg/kg) decline pain and inflammation by downregulating the activation of TNF-R1, TNF-α, IL-1ß, IL-6, NF-κB, oxidative stress markers, and tissue histology. PRACTICAL APPLICATIONS: The research work represents the first report on inhibitory mechanism of NF-κB by pomegranate rind extract, enriched in tannins and flavanoids. The findings of the study provide satisfactory evidence of pomegranate rind in amelioration of adjuvant-induced arthritis. Pomegranate rind, being enrich in bioactive compounds like phenolics and flavanoids possess potent antioxidant activity that might contribute in attenuating rheumatoid arthritis.

Data in support of poisoning related mortalities from southern Himachal Pradesh.

Poisoning has always been pointed as one of the leading causes of human death throughout the world. Despite the best efforts made by many research institutes, the worldwide true figure on mortalities with poisoning could never be achieved due to many reasons. One of the main reasons is the unavailability of complete database from the rural and catchment areas of the world where these types of incidents are usual. People can be made aware about this problem by presenting data articles on regular basis, therefore to mark a resource document these data should be regularly up-dated. The current data report is a briefing of types and trends of chemical poisoning amongst human in southern hilly region of Himachal Pradesh (HP), India. This research database is an outcome of five year retrospective study based on assessment of records pertaining human deaths associated with poisoning occurred in southern Himachal Pradesh, and reported at State Forensic Science Laboratory (SFSL), Junga during 2010-14. Cases where ethyl alcohol was detected have been put under exclusion criterion. All the cases were reviewed and summarized in terms of yearly and monthly frequency of reports wrapping important information portraying the involvement of gender, age, locality, types of poison, and mode of death in the poisoning incidents. Review of these scientific reports showed some notable figures having a direct concern with public and legal domains to promote risk reduction and prevention of chemical poisonings.