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Abstract Neuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer’s disease, which is characterized by the aggregation of pathological tau. One major driver of both age- and tau-associated neuroinflammation is the NF-κB and NLRP3 signaling axis. However, current treatments targeting NF-κB or NLRP3 may have adverse/systemic effects, and most have not been clinically translatable. In this study, we tested the efficacy of a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically targeting both NF-κB and NLRP3 in the brain for reducing neuroinflammation and improving cognitive function in old (aged 19 months) wildtype mice, and in rTg4510 tau pathology mice (aged 2 months). We found that 4 weeks of NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles in the brain and improved cognitive-behavioral function in both old and rTg4510 mice. These effects of NF-κB/NLRP3-targeting Nanoligomers were also associated with reduced glial cell activation and pathology, favorable changes in transcriptome signatures of glia-associated inflammation (reduced) and neuronal health (increased), and positive systemic effects. Collectively, our results provide a basis for future translational studies targeting both NF-κB and NLRP3 in the brain, perhaps using Nanoligomers, to inhibit neuroinflammation and improve cognitive function with aging and neurodegeneration.

Abstract Background By resolving complicated spectra from drug combinations, chemometric techniques are valuable for multi-component investigation. The capacity to properly estimate combinations of components without separating drugs from their mixture is one of the benefits of chemometric analysis approaches over traditional analytical methods. These approaches are easy to use and sensitive even to the lowest concentrations. They are also practical, affordable, and cost-effective. In the current study, the chemometric aided spectrophotometric approach was used to evaluate the two drugs naringin and verapamil. The approach is multidimensional and based on chemometrics, which includes an orthogonal partial least square method that is a new refinement of the partial least squares regression analysis method. With this technique, no conversions are made to the spectrum that overlaps the two drugs. The tools UV-PROBE, SIMCA version 17, and excel were used to process the chemometric data. Results According to results from an orthogonal partial least square model, the mean percent recovery and relative standard deviation for the combination of verapamil with naringin were 100.80/1.19 and 100.836/1.35, respectively.The calibration model was used to predict known synthetic mixtures.This method shows good consistency in recovery ranging between 98.92 and 103.59% for VER and from 96.21 to 101.84% NAR. As saying the synthetic mixture revealed that it had a high percentage of purity. Conclusions The proposed chemometric method can estimate the quantitative amount of pharmaceuticals based on their dosage forms. This approach meets the requirements for the international conference on harmonization's (ICH) analytical criteria, such as precision and accuracy. Graphical Abstract

Background and Objective: Newborn screening (NBS) aims towards early detection of congenital disorders or prevention of intellectual and physical defects and life-threatening illness. Three disorders namely congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and glucose-6-phosphate dehydrogenase deficiency (G-6-PDD) were selected for a preliminary study for NBS. The study aimed to establish NBS in the Indian scenario that could lay a framework for future such initiatives. Methods: A screening programme was conducted at a tertiary care hospital for 1 year. All the neonates born at All India Institute of Medical Sciences (AIIMS), Patna, were screened for their blood levels of glucose-6-phosphate dehydrogenase (G-6-PD), 17-hydroxyprogesterone (17-OHP) and thyroid-stimulating hormone (TSH). Heel-prick blood samples were collected within 48–72 h of birth, and the level of these parameters was accessed by enzyme immunoassay (EIA). Results: A total of 492 neonates were born from January 2020 to December 2020, of which 369 newborns were screened for CAH, CH and G-6-PDD. Of 369 neonates, one case (male) had an increased level of TSH, six cases (all males) had an increased level of 17-OHP and no case was found with G-6-PDD. Interpretation and Conclusions: Preliminary data on the prevalence of various genetic disorders revealed that CAH is the most prevalent disorder followed by CH in the population of Bihar. More efforts need to be undertaken to create awareness and to make screening a successful programme in India. A cost-effective nationwide screening programme is highly recommended for the detection of such cases at the earliest to avoid their future complication.

Introduction Prophylactic laser peripheral iridotomy (LPI) and cataract surgery are considered the primary treatments for primary angle closure suspect (PACS) as they have proven effectiveness in widening the iridocorneal angle and addressing the underlying anatomical issues associated with this condition. The objective of this study is to compare the impact of LPI and cataract surgery on anterior chamber angle parameters, aiming to fill the existing research gap.Methodology A prospective comparative study was conducted, involving 76 eyes of 61 patients. The study focused on patients diagnosed with PACSs and early cataract. The patients received treatment either through LPI or cataract surgery. Comprehensive eye examination was performed, including gonioscopy and anterior segment parameters were measured using anterior segment ocular coherence tomography (ASOCT). Follow-up examinations were conducted at 1 week and 1 month after the procedures, which included ASOCT and gonioscopy performed during the 1-month follow-up.Results All anterior chamber angle parameters increased significantly after treatment in both groups, including trabecular iris angle (TIA), angle opening distance at 250, 500 and 750 µm (AOD 250, AOD500, AOD750), trabecular iris surface area at 500 and 750 µm (TISA500, TISA750) and angle recess area at 500 and 750 µm from scleral spur (ARA500, ARA750) (p

Background: The second wave of COVID-19 was disastrous and claimed many lives in India and abroad. The most challenging task was to provide the required treatment as per the patient’s condition, within a limited span of time. The lack of prognostic predictors at the time of admission led to failure in prioritizing the patient’s need for intensive care. Aim: This study was conducted to find out the clinical and laboratory parameters at the time of admission to ICU as predictors of outcomes in COVID-19 patients, which can help in judicious utilization of the available resources for better patient care. Subjects and Methods: Study comprises of 161 ICU admitted patients. Study of clinical traits, comorbidities, test results, and demographic variables were carried out among survivors and non-survivor. Result: Maximum death were patients of age group 21–30 years and male gender. Mortality in hypertensives, diabetics, and patients with sepsis were found to be statistically significant. Patients who developed ARDS and pneumonia or needed ventilation died invariably. High levels of laboratory parameters like IL-6, LDH, PT, INR, aPTT, ferritin, WBC count, and D-dimer were significantly associated with poor outcomes and at a particular cutoff had optimum sensitivity and specificity to predict mortality in ICU admitted COVID-19 patients. At the same time, low lymphocyte count and PaO2/FiO2 ratio was significantly associated with bad prognosis (P < 0.05). Conclusion: This paper will help in prioritizing patients in ICU who need special attention especially at the time of meager supply of resources.

Tumors are composed of heterogeneous populations of dysregulated cells that grow in specialized niches that support their growth and maintain their properties. Tumor heterogeneity and metastasis are among the major hindrances that exist while treating cancer patients, leading to poor clinical outcomes. Although the factors that determine tumor complexity remain largely unknown, several genotypic and phenotypic changes, including DNA mutations and metabolic reprograming provide cancer cells with a survival advantage over host cells and resistance to therapeutics. Furthermore, the presence of a specific population of cells within the tumor mass, commonly known as cancer stem cells (CSCs), is thought to initiate tumor formation, maintenance, resistance, and recurrence. Therefore, these CSCs have been investigated in detail recently as potential targets to treat cancer and prevent recurrence. Understanding the molecular mechanisms involved in CSC proliferation, self-renewal, and dormancy may provide important clues for developing effective therapeutic strategies. Autophagy, a catabolic process, has long been recognized to regulate various physiological and pathological processes. In addition to regulating cancer cells, recent studies have identified a critical role for autophagy in regulating CSC functions. Autophagy is activated under various adverse conditions and promotes cellular maintenance, survival, and even cell death. Thus, it is intriguing to address whether autophagy promotes or inhibits CSC functions and whether autophagy modulation can be used to regulate CSC functions, either alone or in combination. This review describes the roles of autophagy in the regulation of metabolic functions, proliferation and quiescence of CSCs, and its role during therapeutic stress. The review further highlights the autophagy-associated pathways that could be used to regulate CSCs. Overall, the present review will help to rationalize various translational approaches that involve autophagy-mediated modulation of CSCs in controlling cancer progression, metastasis, and recurrence.

Molecular surveillance of resistance is an increasingly important part of vector borne disease control programmes that utilise insecticides. The visceral leishmaniasis (VL) elimination programme in India uses indoor residual spraying (IRS) with the pyrethroid, alpha-cypermethrin to control Phlebotomus argentipes the vector of Leishmania donovani, the causative agent of VL. Prior long-term use of DDT may have selected for knockdown resistance (kdr) mutants (1014F and S) at the shared DDT and pyrethroid target site, which are common in India and can also cause pyrethroid cross-resistance. We monitored the frequency of these marker mutations over five years from 2017-2021 in sentinel sites in eight districts of north-eastern India covered by IRS. Frequencies varied markedly among the districts, though finer scale variation, among villages within districts, was limited. A pronounced and highly significant increase in resistance-associated genotypes occurred between 2017 and 2018, but with relative stability thereafter, and some reversion toward more susceptible genotypes in 2021. Analyses linked IRS with mutant frequencies suggesting an advantage to more resistant genotypes, especially when pyrethroid was under-sprayed in IRS. However, this advantage did not translate into sustained allele frequency changes over the study period, potentially because of a relatively greater net advantage under field conditions for a wild-type/mutant genotype than projected from laboratory studies and/or high costs of the most resistant genotype. Further work is required to improve calibration of each 1014 genotype with resistance, preferably using operationally relevant measures. The lack of change in resistance mechanism over the span of the study period, coupled with available bioassay data suggesting susceptibility, suggests that resistance has yet to emerge despite intensive IRS. Nevertheless, the advantage of resistance-associated genotypes with IRS and under spraying, suggest that measures to continue monitoring and improvement of spray quality are vital, and consideration of future alternatives to pyrethroids for IRS would be advisable.

A 28-year-old male hospitalized with a diagnosis of acute pancreatitis presented with sudden onset of blurred vision in both eyes after 48 h of admission. Visual acuity was counting fingers in both eyes. Fundus examination revealed multiple cotton wool spots and intraretinal hemorrhages typical of Purtscher’s retinopathy. Optical coherence tomography macula showed serous macular detachment. In 8 weeks follow-up, visual acuity improved to 6/18 oculus dexter (OD) and 6/60 oculus sinister (OS) with resolution of fundus lesions and resorbed subretinal fluid. Purtscher-like retinopathy, though rare should be considered as a differential in all cases with vision loss in acute pancreatitis. This particular case highlights the significance of a thorough examination of the fundus by an ophthalmologist in identifying this infrequent condition that is often overlooked.

Introduction: Nurses are the frontline workers who had to play multiple functions like in acute care, community, etc. but, it was stated that COVID-19 has caused immense trauma to nurses globally. Methods: A descriptive phenomenological study to explore the lived experience of nurses working in COVID-19 units was conducted among nine senior nursing officers recruited by purposive homogenous sampling and interviewed with an open-ended interview guide by ensuring data saturation. COREQ guideline were adopted for this qualitative study. Results: Qualitative data were analysed using Giorgi’s framework, and themes and sub-themes were derived. The major themes that emerged in the present study were "Reactions and preparation", "Feelings and satisfaction in active duty", "Role of a helping hand", "Working experience in PPE", and "Pandemic and socialization". Each theme had further sub-themes to classify the verbatims. Conclusion: Most of the nurses had anxiety and prepared themselves to play with fire, had unrealistic hope, and mixed emotions, kept their family away and intentionally concealed information to reduce family’s fear, were satisfied with training and preparation, and had unpleasant experiences with PPE, had to restrict their social activities and felt social stigma. It also concludes with the recommendation that warrants the need to improve their professional quality of life and working conditions by safeguarding nurses’ physical and mental health.

Hutchinson-Gilford progeria syndrome frequently exhibits stunted growth and premature ageing. Notable ocular characteristics can encompass a large number of ocular abnormalities. Here, we report a case of a 17-year-old female who presented with complaints of a red bump not resolving with medications in her right eye for 3 months. On excisional biopsy, the mass was found to be a pyogenic granuloma. The occurrence of pyogenic granuloma in a patient with progeria is extremely rare. This highlights the importance of considering atypical presentations and potential complications in patients with Hutchinson-Gilford progeria syndrome. This information can assist healthcare professionals in the early recognition and appropriate management of ocular conditions in individuals with Hutchinson-Gilford progeria syndrome.

Purpose: To present a case of extrapulmonary sarcoidosis presenting with ocular and cutaneous involvement. Observations: We report a 54-year-male who presented with bilateral redness of eyes, photophobia, and diminished vision for a week. The best corrected visual acuity in the right eye was 6/60 and the left eye was counting fingers close to face (CFCF). He also had multiple brown plaques on the nape of the neck, chest, back, and arms. Furthermore, he was on multiple antipsychotic drugs for schizophrenia for 3 years. Uveitis investigation workup revealed raised serum angiotensin converting enzyme (ACE), negative Mantoux, and other serological tests. The patient was treated for acute anterior uveitis secondary to sarcoidosis. Clinical improvement was seen after a few days following treatment. The patient presented a year later with multiple yellowish conjunctival nodules in the superior bulbar conjunctiva associated with hyperemia. A biopsy of the plaque like skin lesions was done, which suggested cutaneous sarcoidosis. Involvement of the skin and the eyes raised suspicion that the persistent psychotic episodes despite multiple antipsychotic drugs could be attributed to neurosarcoidosis. However, magnetic Resonance Imaging (MRI) of the brain and orbit showed normal findings. After treatment with corticosteroids and immunosuppressives (methotrexate), the conjunctival nodules as well as skin lesions drastically improved, and the psychosis also responded well to clozapine. Conclusion: A high index of suspicion is needed in cases presenting with granulomatous uveitis with multisystem involvement. Long-term follow-up is crucial to monitor the disease progression and adverse effects of medications.

Background: The etiology of hypercalcemia varies according to the clinical setting. Hitherto, data on the prevalence and profile of hypercalcemia in hospitalized Asian–Indian patients are limited. Hence, we conducted a prospective observational study to determine the prevalence and etiological profile of hypercalcemia in hospitalized Asian–Indian patients and its association with 6-month mortality. Materials and Methods: We conducted a prospective observational study wherein all the patients (aged >12 years) admitted to the general medicine wards of a tertiary care hospital in North India between January 1, 2016, and June 30, 2017, were screened. Finally, patients with sustained hypercalcemia (defined as corrected serum total calcium ≥10.4 mg/dl documented twice at least 24 h apart) were included in this study. These patients were followed up throughout the hospital course and thereafter till 6 months from the date of discharge. Results: Out of 9902 patients, 150 patients had sustained hypercalcemia (prevalence 1.5%). The most common cause of hypercalcemia was malignancy (41.3%), followed by primary hyperparathyroidism (PHPT, 32.7%). Vitamin D intoxication was responsible for hypercalcemia in 8.7% of patients; 2.7% of patients had hypercalcemia of advanced chronic liver disease. Nevertheless, a definite etiology could not be identified in 7.3% of the patients with hypercalcemia. At the end of 6 months of follow-up, the cumulative mortality rate was 28%. Underlying malignancy and higher calcium levels were the significant determinants of mortality. Conclusions: The prevalence of hypercalcemia in Asian–Indian patients admitted to a tertiary care hospital was 1.5%. The most common etiology was malignancy, followed by PHPT.

Healthcare systems deal with disease prevention, early detection, diagnosis, investigation, and timely, affordable, and safe treatment. For the delivery of services in the health sector, communication is the key to linking the service provider and the patients. Mobile technology in the recent past has rendered various platforms of communications for the healthcare system. Thus, in health, mobile technology has greatly contributed to time management and cost reduction for healthcare at every level including hospital visits to individual appointments with doctors, hence the convenience. With advancements in mobile technologies and the growing number of mobile users, newer opportunities have opened up for the use of mobiles for patient care. Emerging information and communication technologies with the help of the Internet of Things (IoT) have been instrumental in integrating different domains of the health sector with mobile technology. Thus, the technology may have the potential to become powerful medical tools to support the health sector at all levels of care. In this review, the concept, applications, and advantages of mobile technology for health and the present pandemic have been discussed. It also discusses mobile health technology, as a support system for convenient and safer healthcare for public health, and the opportunities to improve its applications for unseen future health crises.

Background: The purpose of this study was to evaluate the short-term response of intravitreal bevacizumab in diabetic macular edema (DME) and assess the variation in treatment outcomes in different morphology patterns using spectral domain–optical coherence tomography (SD-OCT). Objective: To study different morphological patterns of DME based on OCT and compare their treatment response to bevacizumab. Methods: Hundred and twelve eyes of 112 patients with DME were included and treated with intravitreal bevacizumab (1.25 mg/0.05 ml monthly for 3 months). The morphological patterns of DME were classified on the basis of OCT into three groups – diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) – and changes in central macular thickness (CMT) and best corrected visual acuity (BCVA) after treatment were compared. Results: A total of 112 eyes with DME were included and consisted of 40 DRT, 37 CME, and 35 SRD. Treatment with bevacizumab resulted in decrease in central macular thickness and improvement in BCVA in all three groups. The baseline visual acuity and CMT of DRT group was better than that of the other two groups. The treatment outcome was measured in terms of CMT and BCVA. Change in CMT was statistically significant among three groups and was found to be better in DRT group ( p

Abstract Introduction Diabetic macular oedema (DME) is one of the major cause of decreased visual acuity in patients with diabetic retinopathy. Poor glycaemic control is associated with increased incidence of DME. Methods A total of 112 eyes of 112 patients were studied in this cross‐sectional study and were classified into three groups based on HbA1c: group 1 included patients with good glycaemic control (HbA1c ≤7%), group 2 included patients with moderate glycaemic control (HbA1c between 7% and 9%) and group 3 included patients with poor glycaemic control (HbA1c ≥9%). Results We included 112 eyes of 112 patients. The mean duration of diabetes mellitus (DM) was 11.37 years. In statistical analysis, CMT (mean 188.80 ± 27.64 μm) positively correlated with mean HbA1c level (7.95 ± 1.29%) (r = 0.238, p

Summary: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans.

BackgroundIn 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016.MethodsEight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS.ResultsComplete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019.ConclusionThrough effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets.

Purpose. To study the clinical spectrum of Vogt-Koyanagi-Harada (VKH) disease in a tertiary eye center in Nepal. Methods. Baseline demographic details and clinical features of six patients diagnosed as VKH in a tertiary eye center were retrospectively reviewed. Examinations included best corrected visual acuity, intraocular pressure, and slit lamp examination of anterior and posterior segments. Baseline blood investigations, chest X-ray, fundus photography, and fundus fluorescent angiography (FFA) were performed on all the patients. Results. The mean age at presentation was 46±8.43 years with female predominance (83.3%). The disease was complete in 16.7%, incomplete in 16.7%, and probable in 66.7% of the patients. Most cases presented in acute uveitis stage (66.7%). The most common finding in acute cases was serous retinal detachment (66.7%), followed by disc edema (58.3%), whereas in chronic cases, depigmented fundus was the most common. All cases had bilateral presentation. Conclusion. VKH is an important cause of bilateral loss of vision and has a good visual prognosis if aggressive treatment is initiated during the early stages.

Sewing professionals are engaged in extensive near work in a small and intensely condensed workspaces, thereby exposing themselves to different ocular and vision-related problems. In a cross-sectional study, 305 sewing professionals of garment factories were included and assessed for ocular and vision-related problems. The assessment included detailed anterior and posterior segment examination and vision assessment comprising of visual acuity, static refraction, dynamic refraction, eye alignment, convergence, fusional vergence, amplitude of accommodation, accommodative facility, color vision, and stereopsis. The findings were recorded on preset proforma and data were analyzed in SPSS version 20. Ocular and Vision-related problems were reported for all participants by descriptive data (number, frequency, median, IQR). The median age of the sewing professional was 30 (24–39) years with male predominance (65.2%). On anterior segment assessment, meibomitis (24.26%) was the most prevalent anterior segment disorder. Prevalence of refractive error was seen in 79.7% of the subjects of which hyperopia (44.5%) was the most prevalent form of refractive error. In participants of age group less than 40 years, 79.5% of the population were found to be consistent with some form of vergence and accommodative disorder; 44.5% manifesting convergence excess with accommodative insufficiency. These participants reported ocular, visual, and asthenopic symptoms at a higher rate as compared to other dysfunctions. Association between vision-related problems and symptoms was analyzed using a Chi-square test. A significance level of 0.05 was applied for a 95% confidence interval. Ocular, visual, and asthenopic symptoms were significantly associated with binocular and accommodative disorders (r = 18.726, p = 0.04). Ocular morbidity and binocular vision anomalies were significantly prevalent in sewing professionals of garment factories.

Objective To study the influence of glycosylated haemoglobin (HbA1c) on response of bevacizumab in patients with diabetic macular oedema.Methods and Analysis A total of 37 eyes of 37 patients with vision loss due to diabetic macular oedema treated with bevacizumab were included in this study. Participants received monthly intravitreal bevacizumab (0.05 mL/1.25 mg) for 3 months.Results There were 17 patients with baseline HbA1c ≤7% (7% (>53mmol/mol) treated with bevacizumab included in the study. The mean improvement in visual acuity at 3 months was 0.50 logMAR in HbA1c ≤7%(7%(>53mmol/mol) group (95% CI,-0.05-0.38; p=0.13). The mean central macular thickness (CMT) reduction was −229.76 µm in patients with a baseline HbA1c ≤7% (7% (>53mmol/mol) (95% CI,12.98-156.14; p=0.022).Conclusion Our study suggests that baseline glycaemic control can affect the treatment outcome of intravitreal bevacizumab in the management of diabetic macular oedema and the response was found to be better in patients with good glycaemic control (low HbA1c).

Cancer stem cells (CSCs) are a small and elusive subpopulation of self-renewing cancer cells with remarkable ability to initiate, propagate, and spread the malignant disease. In addition, they exhibit increased resistance to anticancer therapies, thereby contributing to disease relapse. CSCs are reported to be present in many tumor types such as melanoma, sarcoma, mammary tumors, colon cancer and other solid tumors. These cells from different tumors show unique energetic and metabolic pathways. For example, CSCs from one type of tumor may predominantly use aerobic glycolysis, while from another tumor type may utilize oxidative phosphorylation. Most commonly these cells use fatty acid oxidation and ketone bodies as the main source of energy production. CSCs have a remarkable ability to reprogram their metabolism in order to survive under adverse conditions such as hypoxia, acidosis, and starvation. There is increasing interest to identify molecular targets that can be utilized to kill CSCs and to control their growth. In this review, we discuss how an understanding of the unique metabolism of CSCs from different tumors can offer promising strategies for targeting CSCs and hence to prevent disease relapse and to treat the metastatic disease.

The genetically engineered Chimeric Antigen Receptor bearing T-cell (CAR T cell) therapy has been emerged as the new paradigm of cancer immunotherapy. However, recent studies have reported an increase in the number of relapsed haematological malignancies. This review provides newer insights into how the efficacy of CAR T cells might be increased by the application of new genome editing technologies, monitoring the complexity of tumor types and T cells sub-types. Next, tumor mutation burden along with tumormicroenvironment and epigenetic mechanisms of CAR T cell as well as tumor cell may play a vital role to tackle the cancer resistance mechanisms. These studies highlight the need to consider traditional cancer therapy in conjunction with CAR T cell therapy for relapsed or cases unresponsive to treatment. Of note, this therapy is highly expensive and requires multi-skill for successful implementation, which results in reduction of its accessibility/affordability to the patients. Here, we also propose a model for cost minimization of CAR T cell therapy by a collaboration of academia, hospitals and industry.

Cancer is a leading cause of death worldwide and sustained focus is on the discovery and development of newer and better tolerated anticancer drugs especially from plants. The sulforhodamine B (SRB) in vitro cytotoxicity assay, sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used to investigate the anticancer activity of root extracts of Aristolochia ringens Vahl. (Aristolochiaceae; 馬兜鈴 mǎ dōu líng). AR-A001 (IC50 values of 20 μg/mL, 22 μg/mL, 3 μg/mL, and 24 μg/mL for A549, HCT-116, PC3, and THP-1 cell lines, respectively), and AR-A004 (IC50 values of 26 μg/mL, 19.5 μg/mL, 12 μg/mL, 28 μg/mL, 30 μg/mL, and 22 μg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1, respectively), were observed to be significantly active in vitro. Potency was highest with AR-A001 and AR-A004 for PC3 with IC50 values of 3 μg/mL and 12 μg/mL, respectively. AR-A001 and AR-A004 produced significant (p

ObjectivesThe present study was planned to formulate, characterize and evaluate the pharmacokinetics of a novel "NanoFDC" comprising three commonly prescribed anti-hypertensive drugs, hydrochlorothiazide (a diuretic), candesartan (ARB) and amlodipine (a calcium channel blocker).Basic methodsThe candidate drugs were loaded in Poly (DL-lactide-co-gycolide) (PLGA) by emulsion- diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in vitro release individually. Single dose pharmacokinetic profiles of the nanoformulations alone and in combination, as a NanoFDC, were evaluated in Wistar rats.ResultsThe candidate drugs encapsulated inside PLGA showed entrapment efficiencies ranging from 30%, 33.5% and 32% for hydrochlorothiazide, candesartan and amlodipine respectively. The nanoparticles ranged in size from 110 to 180 nm. In vitro release profile of the nanoformulation showed 100% release by day 6 in the physiological pH 7.4 set up with PBS (phosphate buffer saline) and by day 4-5 in the intestinal pH 1.2 and 8.0 set up SGF (simulated gastric fluid) and SIF (simulated intestinal fluid) respectively. In pharmacokinetic analysis a sustained-release for 6 days and significant increase in the mean residence time (MRT), as compared to the respective free drugs was noted [MRT of amlodipine, hydrochlorothiazide and candesartan changed from 8.9 to 80.59 hours, 11 to 69.20 hours and 9 to 101.49 hours respectively].ConclusionWe have shown for the first time that encapsulating amlodipine, hydrochlorothiazide and candesartan into a single nanoformulation, to get the "NanoFDC (Fixed Dose Combination)" is a feasible strategy which aims to decrease pill burden.