Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Effectiveness of ayurvedic formulation, NAOQ19 along with standard care in the treatment of mild-moderate COVID-19 patients: A double blind, randomized, placebo-controlled, multicentric trial.

BACKGROUND: Medicines in indigenous systems such as Ayurveda have strong antimicrobial activity but double-blind randomized control trials are infrequent in this system of medicine. The efficacy of a new ayurvedic formulation was evaluated during the pandemic. METHODS: 150 mild-moderate COVID-19 patients were enrolled and randomized in 1:1 to NAOQ19 and placebo group. RT-PCR was done on Day 3, 5 and 7. CBC, CRP, LFT, and KFT were assessed at baseline and exit. Duration of hospital stay was noted and clinical assessment was also performed. RESULT: The results demonstrated more people turning RT-PCR negative in the NAOQ19 group compared to the placebo group on day 3 (p-value = 0.033). The mean time duration to turn RT-PCR negative was significantly lower in the NAOQ19 group (4.6 days) compared to placebo group (5.2 days) (p-value = 0.018). There was significant reduction in hospital stay among patients in the NAOQ19 arm who were discharged earlier (5.6 days) compared to placebo group (6.4 days) (p-value = 0.046). Patients in NAOQ19 arm did not show any adverse life-threatening events. CONCLUSION: The ayurvedic preparation given along with standard of care therapy reduced the duration of hospital stay and there was earlier conversion to RT-PCR negative.The integrated approach can help to reduce patient workload in the hospitals as well as limit the transmission of the virus in the community. STUDY REGISTRATION: CTRI/2021/05/033790.

Sustainable approach for adsorptive removal of cationic and anionic dyes by titanium oxide nanoparticles synthesized biogenically using algal extract ofSpirulina.

Worldwide, dyes are significant pollutants present in water because of their huge consumption for industrial purposes. These dyes as pollutants cause serious health issues in human beings and cause the loss of aquatic biodiversity. So, remediation of pollutants like dyes from wastewater is the need of the hour. In the present study, we greenly synthesizedSpirulina-mediated titanium oxide nanoparticles (STONPs) for the adsorptive remediation of methyl orange (MO) (anionic) and malachite green (MG) (cationic) dyes. The characterization of STONPs was performed by Field emission scanning electron microscopy (FESEM) with EDX, FT-IR, XRD, Zeta Potential and particle size analyzer, Raman spectroscopy, and UV-vis. The various parameter effects like pH, nano-adsorbent dose, the concentration of dye, contact time, and temperature were also examined. Adsorption isotherms like Langmuir, Freundlich, and Temkin, and Kinetics models like Elovich Model, Pseudo 1st, intraparticle diffusion model (IPDM), Pseudo 2nd order, and the thermodynamic model were applied for a stronger interpretation. Theqmaxattained utilizing the Langmuir adsorption model was 272.4795 mg g-1and 209.6436 mg g-1for MO and MG correspondingly. The regeneration study of synthesized nanomaterials up to five cycles was also done. We found that greenly synthesized STONPs have great potential for adsorptive remediation for both MG and MO dyes.

Study of anaemia in pregnancy and low birth weight in fluoride endemic area of Western Rajasthan: a cohort study.

Background: Fluoride is a noxious element known to destroy gastrointestinal mucosa, leading to erythrocytes' destruction and causing anaemia. The birth weight of newborn babies is a significant indicator of a child's vulnerability to the risk of childhood diseases and chances of existence. Methods: This prospective cohort study was planned to find linkages between fluorosis and the low-birth weight of newborn babies with anaemic mothers. Antenatal mothers until the 20th week of gestation were followed up till delivery in the Antenatal Clinic of a District Hospital in one of the known fluoride-endemic districts (Nagaur) and the other not-so-endemic district (Jodhpur) of Western Rajasthan. Results: Around 19% of the newborn in Jodhpur and around 22% in Nagaur had low birth weight. Mean fluoride values in water samples were measured to be 0.57 (range from 0.0 to 2.7 PPM) in Jodhpur and 0.7 (range from 0.0 to 3.4 PPM) in Nagaur. Conclusions: Thus, in fluoride endemic areas, other factors should be included besides iron and folic acid supplementation for improving anaemia in pregnant women. This calls for assessing the effectiveness of de-fluoridation activities along with the area's most common indigenous food practices.

Onion waste based-biorefinery for sustainable generation of value-added products.

Waste derived from the onion processing sector can be harnessed for the production of organic acids, polyphenols, polysachharides, biofuels and pigments. To sustainably utilize onion processing residues, different biorefinery strategies such as enzymatic hydrolysis, fermentation and hydrothermal carbonization have been widely investigated. This review discusses the recent advances in the biorefinery approaches used for valorization of onion processing waste followed by the production of different value-added products from diverse classes of onion waste. The review also highlights the current challenges faced by the bioprocessing sector for the utilization of onion processing waste and perspectives to tackle them.

QSAR, Molecular Docking, MD Simulation and MMGBSA Calculations Approaches to Recognize Concealed Pharmacophoric Features Requisite for the Optimization of ALK Tyrosine Kinase Inhibitors as Anticancer Leads.

ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm−multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R2 = 0.69−0.87, F = 403.46−292.11, etc., internal validation parameters; Q2LOO = 0.69−0.86, Q2LMO = 0.69−0.86, CCCcv = 0.82−0.93, etc., or external validation parameters Q2F1 = 0.64−0.82, Q2F2 = 0.63−0.82, Q2F3 = 0.65−0.81, R2ext = 0.65−0.83 including RMSEtr < RMSEcv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.

A socio-ecological critique on India's local health traditions amidst rising incidence of global pandemics.

Introduction: The COVID-19 crisis has exposed inadequacy to deal with such health emergencies. The state of healthcare facilities in India is shambolic, which is further exacerbated by the exclusivity of modern health systems. The authors argue for vertical and horizontal expansion of the existing system to include traditional medicine systems, in favor of an urgently needed holistic and more inclusive healthcare system. Methods: Secondary data were collected from free online resources, including preprints, reprints and databases, J-gate Plus, PubMed and Web of Science, using keywords such as, "folk medicine", "folk medicine AND India", "traditional Indian medicines", "indigenous Indian medicines AND India", "Indian ethnomedicines", "Indian AND folk AND medicine", "indigenous Indian medicine". Results and conclusions: Insufficiently robust public healthcare infrastructure, lack of enough qualified health professionals, and poor use of its traditional medicinal systems, are limiting the access of basic healthcare facilities to a large section of the Indian population. Despite vehement opposition and criticism from modern health system practitioners, indigenous and local healing traditions do offer benefits and share a common global goal of health and healing. The objectives of Universal Health Coverage and Health for All as enshrined in the Sustainable Development Goals (SDGs) cannot be achieved without their involvement, especially in remote and economically disadvantaged regions of the country. Even a sub-optimal utilization of its biological and human resources and related traditional knowledge can not only profoundly change the health, but also the economic landscape of India. Here, we have nuanced the constrains posed by the emerging health challenges, status and prospects of the great and little traditions of the Indian System of Medicines in fulfilling the urgent healthcare needs of the country. The authors based their arguments on the available evidence, rather than emotive ideas or, as a fan of Indian traditional medicines, and suggest for the purposeful inclusion of traditional health systems and practitioners more actively in India's health care delivery systems. The country must not squander the opportunities offered by its traditional medicinal systems.

800 IU versus 400 IU per day of vitamin D3 in term breastfed infants: a randomized controlled trial from an LMIC.

This open-label, block-randomized controlled trial compared the effect of 800 IU/day and 400 IU/day of oral vitamin D3 supplementation in reducing vitamin D insufficiency (VDI) among healthy-term breastfed infants at 14 weeks of postnatal age. All eligible infants were randomized to receive either 800 or 400 IU/day of oral vitamin D3 (starting within the first week until 14 weeks). The primary outcome was the proportion of infants with VDI (25-OH-D < 20 ng/ml) at 14 weeks. Secondary outcomes were vitamin D deficiency (VDD, < 12 ng/ml), severe VDD (< 5 ng/ml), anthropometry, biochemical or clinical rickets, and any adverse events related to vitamin D toxicity (VDT). Among 102 enrolled infants, the distribution of baseline variables (including cord 25-OH-D levels; 13.0 versus 14.2 ng/ml) was similar in both groups. On intention-to-treat analysis, the proportions of infants with VDI at 14 weeks were significantly lower in the 800 IU group compared to those in the 400 IU group [24% versus 55%; RR 0.44; 95% CI: 0.25-0.76]. The proportions of infants with elevated parathormone (6% versus 26.5%; p = 0.012) and severe VDD (0% versus 12.2%; p = 0.033) were significantly lower in the 800 IU group. Clinical rickets developed in three (6.2%) infants in the 400 IU group. No infant developed VDT.      Conclusions: Daily oral supplementation with 800 IU of vitamin D3 resulted in an almost 50% reduction in the proportion of infants with VDI and prevented the occurrence of severe VDD at 14 weeks of age compared to 400 IU with no evidence of vitamin D toxicity.     Trial Registration: Clinical Trial Registry of India (CTRI/2019/02/017374). What is Known: • Breastfeeding is the ideal source of nutrition for healthy-term breastfed infants; however, vitamin D content of breastmilk is suboptimal. • AAP recommends daily oral supplementation of 400 IU of vitamin D to all healthy-term breastfed infants; however, trials from high-income countries support insufficiency of this dose in maintaining serum 25-OH-D levels >20 ng/ml with no such information from low-middle-income countries. What is New: • 800 IU/day of oral vitamin D3 supplementation among term breastfed infants significantly reduces vitamin D insufficiency at 14 weeks' age as compared to the recommended dose of 400 IU/day. • This higher supplemental dose is safe with no evidence of vitamin D toxicity.

Association of miR-155, miR-187 and Inflammatory Cytokines IL-6, IL-10 and TNF-α in Chronic Opium Abusers.

Substance use disorders are known to be associated with inflammation. However, the dynamics of inflammatory cytokines and microRNA in chronic opium use is yet unexplored. The current study determined the levels of inflammatory cytokines TNF-α, IL-6, IL-10 and immune-regulatory miR-155 and miR-187 expressions in chronic opioid use disorder. Adults (n = 48) meeting the 5th Edition of the DSM criteria regarding opioid use disorder and healthy controls (n = 46) were included in the study. Inflammatory cytokines IL-10, IL-6, and TNF-α were analyzed from serum samples, and peripheral blood mononuclear cells processed for miRNA expression. Cases showed significantly raised IL-10 and TNF-α and reduced IL-6. Dose-dependent upregulation of miR-155-5p and miR-187-5p was evident at opium dose >1500 g/month, with a corresponding increase of TNF-α and IL-10. MiR-155 showed a significant positive correlation with IL-6 and TNF-α levels, while miR-187 showed a significant negative association with TNF-α at ≥1000 g/month consumption. Therefore, increasing consumption of opium probably enhances inflammation leading to immunomodulation and aberrant expression of hsa-miR-155-5p and hsa-miR-187-5p in opioid use disorder.

Selenium, oxidative stress and inflammatory markers in handicraft workers occupationally exposed to lead.

Occupational Lead (Pb) exposure increases reactive oxygen species and has been reported to impact inflammatory response by modulating intracellular signaling pathways. Selenium (Se) a vital component of the antioxidant system that plays an important role in modulating cytokines. The present study evaluated Se, malondialdehyde (MDA), total antioxidant capacity (TAC) and cytokines (IL-6, TNF-α, IL-10, IL-17a) in 81 Pb exposed male workers. The median (range) of blood lead level (BLL) and Se were 5 (0.50-31.76) µg/dL and 104 (46.9-189.6) µg/L respectively. The Se, TAC levels were decreased, and MDA, IL-6 levels were increased in the high Pb group (>5µg/dL). Blood lead level independently predicted oxidative stress and antioxidant status. Selenium, TAC levels negatively and MDA, IL-6 levels positively correlated with BLL. Association of Se with IL-6 and TAC suggests some probable role of Se in the underlined mechanism of Pb toxicity.

Specificity Matters: Unpacking Impact Pathways of Individual Interventions within Bundled Packages Helps Interpret the Limited Impacts of a Maternal Nutrition Intervention in India.

BACKGROUND: To address gaps in coverage and quality of nutrition services, Alive & Thrive (A&T) strengthened the delivery of maternal nutrition interventions through government antenatal care (ANC) services in Uttar Pradesh, India. The impact evaluation of the A&T interventions compared intensive ANC (I-ANC) with standard ANC (S-ANC) areas and found modest impacts on micronutrient supplementation, dietary diversity, and weight-gain monitoring. OBJECTIVES: This study examined intervention-specific program impact pathways (PIPs) and identified reasons for limited impacts of the A&T maternal nutrition intervention package. METHODS: We used mixed methods: frontline worker (FLW) surveys (n = ∼500), counseling observations (n = 407), and qualitative in-depth interviews with FLWs, supervisors, and block-level staff (n = 59). We assessed 7 PIP domains: training and materials, knowledge, supportive supervision, supply chains, data use, service delivery, and counseling. RESULTS: Exposure to training improved in both I-ANC and S-ANC areas with more job aids used in I-ANC compared with S-ANC (90% compared with 70%), but gaps remained for training content and refresher trainings. FLWs' knowledge improvement was higher in I-ANC than S-ANC (22-36 percentage points), but knowledge of micronutrient supplement benefits and recommended foods was insufficient (<50%). Most FLWs received supervision (>90%), but supportive supervision was limited by staff vacancies and competing work priorities. Supplies of iron-folic acid and calcium supplements were low in both areas (30-50% stock-outs). Use of monitoring data during review meetings was higher in I-ANC than S-ANC (52% compared with 36%) but was constrained by time, understanding, and data quality. Service provision improved in both I-ANC and S-ANC areas, but counseling on supplement benefits and weight-gain monitoring was low (30-40%). CONCLUSIONS: Systems-strengthening efforts improved maternal nutrition interventions in ANC, but gaps remained. Taking an intervention-specific perspective to the PIP analysis in this package of services was critical to understand how common and specific barriers influenced overall program impact.

Does dehydroepiandrosterone sulfate have a role in COVID-19 prognosis and treatment?

The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.

Association of newborn blood lead concentration with neurodevelopment outcome in early infancy.

BACKGROUND: In utero exposure to toxic metal substances can cause severe neurodevelopmental deficits in developing fetus and infant. METHODS: We evaluated the association of newborn umbilical cord blood lead concentration with early neurodevelopmental performance (cognitive, receptive language, expressive language, fine motor, gross motor and social-emotional development). The Bayley Scale of Infants Developments-III (BSID-III) was used to perform neurodevelopment outcomes at an average age of 6.5 months. In this prospective study, total of 167 mother-child pairs were enrolled from Western Rajasthan, India. Association between risk factors of lead contamination and newborn umbilical cord blood lead levels was observed. Multivariate regression was performed to see the association of cord blood lead level with infant neurodevelopment outcome. RESULTS: The obtained newborn umbilical cord blood lead concentration 5.0-10.5 µg/dL was negatively associated with the sub-scale score of gross motor development (ß-coefficient with 95 % CI; -0.29 (-5.0-0.11), p = 0.04). However, no associations were found with the score of cognitive, language, gross motor, and social-emotional development. The umbilical cord blood lead concentration <5.0 µg/dL was also not associated with the BSID-III scores. The mother's regular intake of calcium supplements during the antenatal period was significantly associated with a lower umbilical cord blood lead level (p-value 0.031). CONCLUSION: The data suggest that newborn umbilical cord blood lead concentration 0.5-10.5 µg/dL has a negative association with early gross motor development during infancy.

Strengthening Nutrition Interventions in Antenatal Care Services Affects Dietary Intake, Micronutrient Intake, Gestational Weight Gain, and Breastfeeding in Uttar Pradesh, India: Results of a Cluster-Randomized Program Evaluation.

BACKGROUND: Maternal nutrition interventions are inadequately integrated into antenatal care (ANC). Alive & Thrive aimed to strengthen delivery of micronutrient supplements and intensify interpersonal counseling and community mobilization through government ANC services. OBJECTIVES: We compared nutrition-intensified ANC (I-ANC) with standard ANC (S-ANC) on coverage of nutrition interventions and maternal nutrition practices. METHODS: We used a cluster-randomized design with cross-sectional baseline (2017) and endline (2019) surveys (n ∼660 pregnant and 1800 recently delivered women per survey) and a repeated-measures longitudinal study in 2018-2019 (n = 400). We derived difference-in-difference effect estimates (DIDs) for diet diversity, consumption of micronutrient supplements, weight monitoring, and early breastfeeding practices. RESULTS: Despite substantial secular improvements in service coverage from India's national nutrition program, women in the I-ANC arm received more home visits [DID: 7-14 percentage points (pp)] and counseling on core nutrition messages (DID: 10-23 pp) than in the S-ANC arm. One-third of women got ≥3 home visits and one-fourth received ≥4 ANC check-ups in the I-ANC arm. Improvements were greater in the I-ANC arm than in the S-ANC arm for any receipt and consumption of iron-folic acid (DID: 7.5 pp and 9.5 pp, respectively) and calcium supplements (DID: 14.1 pp and 11.5 pp, respectively). Exclusive breastfeeding improved (DID: 7.5 pp) but early initiation of breastfeeding did not. Maternal food group consumption (∼4 food groups) and probability of adequacy of micronutrients (∼20%) remained low in both arms. Repeated-measures longitudinal analyses showed similar results, with additional impact on consumption of vitamin A-rich foods (10 pp, 11 g/d), other vegetables and fruits (22-29 g/d), and gestational weight gain (0.4 kg). CONCLUSIONS: Intensifying nutrition in government ANC services improved maternal nutrition practices even with strong secular trends in service coverage. Dietary diversity, supplement consumption, and breastfeeding practices remained suboptimal. Achieving greater behavior changes will require strengthening the delivery and use of maternal nutrition services integrated into ANC services in the health system. This trial was registered at clinicaltrials.gov as NCT03378141.

Use of Complementary and Alternative Medicine (CAM) and Home Remedies by COVID-19 Patients: A Telephonic Survey.

COVID-19 is caused by a novel coronavirus which was first reported in Wuhan city, China. The pandemic has led to considerable mortality globally. India, at present has the second largest burden of COVID-19 cases globally. Clinical trials with new interventions, including new vaccine candidates are being explored in the scientific world. Countries like China and India, with a rich history of traditional medicine, are exploring the effectiveness of traditional medicines to treat COVID-19. This study included 725 patients from an Isolation center, of which 230 (31.7%) were excluded due to reasons like incorrect phone numbers, no response on phone, or denying consent to participate. Finally, 495 participants had responded, of which 367 (74.1%) had not used any Complementary and Alternative Medicine (CAM) product or home remedies while 128 (25.8%) people used 161 CAM products and home remedies during the treatment and even afterward. More than half of the participants (59.6%) among them had consumed Ayurvedic Kadha. Many respondents consumed more than one CAM products or home remedies but there were no reported acute or severe adverse effects with these products. However, it is essential to ensure the safety of these interventions on long-term use because patients with other comorbidities can have a detrimental effect due to these products or due to drug herb interaction with their ongoing medications. Hence, long-term follow-up studies of recovered patients are crucial in determining the effects of medications or CAM products on organ functions due to disease or interventions.

Prevalence of Zinc Deficiency and the Effect of Zinc Supplementation on the Prevention of Acute Respiratory Infections.

OBJECTIVE: Acute lower respiratory infections are an important cause of morbidity and mortality in developing countries. Recent randomized trials of zinc supplementation for the prevention of acute lower respiratory tract infections have revealed discrepant findings. The main aim of this study was to evaluate the prevalence of zinc deficiency and the effect of zinc supplementation on respiratory infections. MATERIAL AND METHODS: A single center, prospective open-label interventional single-arm pre-post study of the effect of oral zinc supplementation in zinc deficient children aged 6 months to 5 years was done. A total of 465 healthy children of age 6 months to 5 years were enrolled in the study for estimation of the prevalence of zinc deficiency. Children having zinc deficiency were recruited to study the efficacy and safety of oral administration of 20 mg zinc for two weeks during a 6-month follow-up period. RESULTS: There were statistically significant differences between the zinc deficient and non-deficient groups according to modified Kuppuswamy categorization of family status and exclusive breast feeding. There was significant difference in the mid arm circumference between the zinc deficient and non-deficient groups (p<0.001). There was significant difference (p<0.001) in the number of episodes of acute upper respiratory infections (AURI), mean duration of AURI, and acute lower respiratory infections (ALRI) between the two groups. There was no significant difference in the ALRI episodes between the two groups. After zinc supplementation in zinc deficient children, there was significant decrease in the number of episodes and mean duration of AURI (p<0.001) and ALRI (p<0.001) within six months after supplementation as compared with the preceding six months before supplementation. CONCLUSION: This study reveals that a short course of zinc supplementation may reduce the burden of AURI/ALRI among the zinc deficient children, but larger studies are needed.

Combinatorial Effect of DCA and Let-7a on Triple-Negative MDA-MB-231 Cells: A Metabolic Approach of Treatment.

Dichloroacetate (DCA) is a metabolic modulator that inhibits pyruvate dehydrogenase activity and promotes the influx of pyruvate into the tricarboxylic acid cycle for complete oxidation of glucose. DCA stimulates oxidative phosphorylation (OXPHOS) more than glycolysis by altering the morphology of the mitochondria and supports mitochondrial apoptosis. As a consequence, DCA induces apoptosis in cancer cells and inhibits the proliferation of cancer cells. Recently, the role of miRNAs has been reported in regulating gene expression at the transcriptional level and also in reprogramming energy metabolism. In this article, we indicate that DCA treatment leads to the upregulation of let-7a expression, but DCA-induced cancer cell death is independent of let-7a. We observed that the combined effect of DCA and let-7a induces apoptosis, reduces reactive oxygen species generation and autophagy, and stimulates mitochondrial biogenesis. This was later accompanied by stimulation of OXPHOS in combined treatment and was thus involved in metabolic reprogramming of MDA-MB-231 cells.

An Update on the Links Between Periodontal Health and General Health.

It should come as no surprise to the reader that the oral cavity, including the periodontal tissues, are not somehow disjointed from the rest of the body. In this paper, we will explore the links between the periodontal and general health of our patients in both directions. That is to say we will explore how someone's general or systemic health conditions/habits are likely to affect their periodontal health, and how someone's periodontal health is likely to affect their systemic health.
Before exploring these links, we will discuss the distinction between an association and a causal relationship, which is a subtle but vital distinction to make. We will then discuss the role of systemic conditions/habits such as diabetes, smoking, diet and stress on the periodontal health of individuals. Following from this, we will discuss the potential influence of the periodontal health of our patients on their systemic health, focussing on the more established links with diabetes and cardiovascular diseases as well as exploring the mechanisms by which these links may exist.
We will conclude with some tips on the holistic care of our patients, incorporating changes that will benefit their oral and systemic health.

Spherically shaped pectin-g-poly(amidoxime)-Fe complex: A promising innovative pathway to tailor a new material in high amidoxime functionalization for fluoride adsorption.

Pectin was hydrolyzed and was processed in spherically-shaped structure through calcium crosslinker. The synthesized spherical-bead structure was surface functionalized by acrylonitrile grafting reaction, which extends the applications of pectin followed by derivatization with hydroxylamine. The matrix was further decorated with the iron metal to enhance the practical applicability in the aqueous system. The chemical structures were characterized via gravimetric analysis, FTIR, SEM-EDX, elemental analysis, XPS and XRD. The results supported the exceptional uniformity with the presence of substantial receptor amidoxime groups in morphology and elemental composition. The process of adsorption was concluded with good adsorption capacity with iron-impregnated-amidoxime. The presence of S2O32-, SO42-, and NO3- had an insignificant influence on fluoride uptake excluding Cl- and PO43- in a binary/mixture solutions. The adsorption data were excellently expressed by the Freundlich isotherm model (R2 > 0.998) which suggests that the surface of the ligand is multifunctional. The kinetic data was determined and pseudo-second-order rate equation showed well-fit (R2 > 0.998) to the presented data. The findings indicate that Fe-impregnated poly(amidoxime) is a cost-effective and eco-friendly promising adsorbent for fluoride removal even at trace level and a wide optimum pH range due to better aqueous dispersibility of pendent groups responsible for the sorption application.