Nutrient patterns and risk of diabetes mellitus type 2: a case-control study.

BACKGROUNDS: Although the significance of diet in preventing or managing diabetes complications is highlighted in current literature, there is insufficient evidence regarding the correlation between nutrient patterns and these complications. The objective of this case-control study is to investigate this relationship by analyzing the dietary intake of nutrients in participants with and without type 2 diabetes (T2D). METHODS: A case-control study was conducted at the Tabriz Center of Metabolism and Endocrinology to investigate the relationship between nutrient patterns and type 2 diabetes (T2D). The study enrolled 225 newly diagnosed cases of T2D and 225 controls. The dietary intake of nutrients was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Principal component analysis using Varimax rotation was used to obtain nutrient patterns. Logistic regression analysis was performed to estimate the risk of T2D. RESULTS: The participants' mean (SD) age and BMI were 39.8 (8.8) years and 27.8 (3.6) kg/m2, respectively. The results identified three major nutrient patterns. The first nutrient pattern was characterized by high consumption of sucrose, animal protein, vitamin E, vitamin B1, vitamin B12, calcium, phosphorus, zinc, and potassium. The second nutrient pattern included fiber, plant protein, vitamin D, Riboflavin, Vitamin B5, copper, and Magnesium. The third nutrient pattern was characterized by fiber, plant protein, vitamin A, riboflavin, vitamin C, calcium, and potassium. Individuals in the highest tertile of nutrient pattern 3 (NP3) had a lower risk of T2D compared to those in the lowest tertile after adjusting for confounders. The odds ratio was 0.52 with a 95% confidence interval of 0.30-0.89 and a P_trend of 0.039. CONCLUSION: This study found that conforming to a nutrient pattern consisting of plant protein, vitamin C, vitamin A, vitamin B2, potassium, and calcium is linked to a lower likelihood of developing T2D.The initial results suggest that following a nutrient pattern that includes these nutrients may reduce the risk of T2D. However, further research is required to confirm the relationship between nutrient patterns and T2D.

Aryl Hydrocarbon Receptor Regulates Muc2 Production Independently of IL-22 during Colitis.

We previously reported that an aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective at reducing colitis severity through immune cell-mediated interleukin-22 (IL-22) production. Intestinal epithelial cells (IECs) are also involved in regulating colitis, so we investigated their AhR-mediated mechanisms in the current report. A transcriptome analysis of IECs in wildtype (WT) mice revealed that during colitis, I3C regulated select mucin proteins, which could be attributed to goblet cell development. To address this, experiments under in vivo colitis (mice) or in vitro colon organoid conditions were undertaken to determine how select mucin proteins were altered in the absence or presence of AhR in IECs during I3C treatment. Comparing WT to IEC-specific AhR knockout mice (AhRΔIEC), the results showed that AhR expression was essential in IECs for I3C-mediated protection during colitis. AhR-deficiency also impaired mucin protein expression, particularly mucin 2 (Muc2), independently of IL-22. Collectively, this report highlights the important role of AhR in direct regulation of Muc2. These results provide justification for future studies aimed at determining how AhR might regulate select mucins through mechanisms such as direct transcription binding to enhance production.

Design and pilot implementation for the BETTER CARE-HF trial: A pragmatic cluster-randomized controlled trial comparing two targeted approaches to ambulatory clinical decision support for cardiologists.

BACKGROUND: Beart failure with reduced ejection fraction (HFrEF) is a leading cause of morbidity and mortality. However, shortfalls in prescribing of proven therapies, particularly mineralocorticoid receptor antagonist (MRA) therapy, account for several thousand preventable deaths per year nationwide. Electronic clinical decision support (CDS) is a potential low-cost and scalable solution to improve prescribing of therapies. However, the optimal timing and format of CDS tools is unknown. METHODS AND RESULTS: We developed two targeted CDS tools to inform cardiologists of gaps in MRA therapy for patients with HFrEF and without contraindication to MRA therapy: (1) an alert that notifies cardiologists at the time of patient visit, and (2) an automated electronic message that allows for review between visits. We designed these tools using an established CDS framework and findings from semistructured interviews with cardiologists. We then pilot tested both CDS tools (n = 596 patients) and further enhanced them based on additional semistructured interviews (n = 11 cardiologists). The message was modified to reduce the number of patients listed, include future visits, and list date of next visit. The alert was modified to improve noticeability, reduce extraneous information on guidelines, and include key information on contraindications. CONCLUSIONS: The BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) trial aims to compare the effectiveness of the alert vs. the automated message vs. usual care on the primary outcome of MRA prescribing. To our knowledge, no study has directly compared the efficacy of these two different types of electronic CDS interventions. If effective, our findings can be rapidly disseminated to improve morbidity and mortality for patients with HFrEF, and can also inform the development of future CDS interventions for other disease states. (Trial registration: Clinicaltrials.gov NCT05275920).

Protocolized Urine Sampling is Associated with Reduced Catheter-associated Urinary Tract Infections: A Pre- and Postintervention Study.

BACKGROUND: Standard urine sampling and testing techniques do not mitigate against detection of colonization, resulting in false positive catheter-associated urinary tract infections (CAUTI). We aimed to evaluate whether a novel protocol for urine sampling and testing reduces rates of CAUTI. METHODS: A preintervention and postintervention study with a contemporaneous control group was conducted at 2 campuses (test and control) of the same academic medical center. The test campus implemented a protocol requiring urinary catheter removal prior to urine sampling from a new catheter or sterile straight catheterization, along with urine bacteria and pyuria screening prior to culture. Primary outcomes were test campus CAUTI rates, compared between each 9-month pre- and postintervention epoch. Secondary outcomes included the percent reductions in CAUTI rates, compared between the test campus and a propensity score-matched cohort at the control campus. RESULTS: A total of 7991 patients from the test campus were included in the primary analysis, and 4264 were included in the propensity score-matched secondary analysis. In the primary analysis, the number of CAUTI cases per 1000 patients was reduced by 77% (6.6 to 1.5), the number of CAUTI cases per 1000 catheter days was reduced by 63% (5.9 to 2.2), and the number of urinary catheter days per patient was reduced by 37% (1.1 to 0.69; all P values ≤ .001). In the propensity score-matched analysis, the number of CAUTI cases per 1000 patients was reduced by 82% at the test campus, versus 57% at the control campus; the number of CAUTI cases per 1000 catheter days declined by 68% versus 57%, respectively; and the number of urinary catheter days per patient decreased by 44% versus 1%, respectively (all P values < .001). CONCLUSIONS: Protocolized urine sampling and testing aimed at minimizing contamination by colonization was associated with significantly reduced CAUTI infection rates and urinary catheter days.

Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting oxidative stress and inflammation.

Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter's 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.

Essential oil from waste leaves of Curcuma longa L. alleviates skin inflammation.

BACKGROUND: Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation. METHODS: EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation. CONCLUSION: These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.

Diarylheptanoids Rich Fraction of Alnus nepalensis Attenuates Malaria Pathogenesis: In-vitro and In-vivo Study.

Diarylheptanoids from Alnus nepalensis leaves have been reported for promising activity against filariasis, a mosquito-borne disease, and this has prompted us to investigate its anti-malarial and safety profile using in-vitro and in-vivo bioassays. A. nepalensis leaf extracts were tested in-vitro against chloroquine-sensitive Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase activity. Among all, the chloroform extract (ANC) has shown promising anti-plasmodial activity (IC50 8.06 ± 0.26 µg/mL). HPLC analysis of ANC showed the presence of diarylheptanoids. Efficacy and safety of ANC were further validated in in-vivo system using Plasmodium berghei-induced malaria model and acute oral toxicity in mice. Malaria was induced by intra-peritoneal injection of P. berghei infected red blood cells to the female Balb/c mice. ANC was administered orally at doses of 100 and 300 mg/kg/day following Peter's 4 day suppression test. Oral administration of ANC showed significant reduction of parasitaemia and increase in mean survival time. It also attributed to inhibition of the parasite induced pro-inflammatory cytokines as well as afford to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. In-vivo safety evaluation study revealed that ANC is non-toxic at higher concentration. Copyright © 2016 John Wiley & Sons, Ltd.

Resident physicians using modern practices for excellent documentation and care in heart failure (PUMPED CHF).

The most common indication for readmission among Medicare patients is congestive heart failure (CHF). Prior studies underscore the use of residents to bolster hospital-wide programs and reduce CHF readmissions. The authors assessed the effectiveness of a novel online training program designed to improve resident documentation and knowledge related to CHF. The findings suggest that despite a significant increase in knowledge scores following the online educational course, there was only a slight increase in documentation scores. Additional teaching modalities need to be identified to foster resident education and create sustained behavior change.

Impact of Visit Volume on the Effectiveness of Electronic Tools to Improve Heart Failure Care.

BACKGROUND: Electronic health record (EHR) tools can improve prescribing of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), but their effectiveness may vary by physician workload. OBJECTIVES: This paper aims to assess whether physician workload modifies the effectiveness of EHR tools for HFrEF. METHODS: This was a prespecified subgroup analysis of the BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) cluster-randomized trial, which compared effectiveness of an alert vs message vs usual care on prescribing of mineralocorticoid antagonists (MRAs). The trial included adults with HFrEF seen in cardiology offices who were eligible for and not prescribed MRAs. Visit volume was defined at the cardiologist-level as number of visits per 6-month study period (high = upper tertile vs non-high = remaining). Analysis at the patient-level used likelihood ratio test for interaction with log-binomial models. RESULTS: Among 2,211 patients seen by 174 cardiologists, 932 (42.2%) were seen by high-volume cardiologists (median: 1,853; Q1-Q3: 1,637-2,225 visits/6 mo; and median: 10; Q1-Q3: 9-12 visits/half-day). MRA was prescribed to 5.5% in the high-volume vs 14.8% in the non-high-volume groups in the usual care arm, 10.3% vs 19.6% in the message arm, and 31.2% vs 28.2% in the alert arm, respectively. Visit volume modified treatment effect (P for interaction = 0.02) such that the alert was more effective in the high-volume group (relative risk: 5.16; 95% CI: 2.57-10.4) than the non-high-volume group (relative risk: 1.93; 95% CI: 1.29-2.90). CONCLUSIONS: An EHR-embedded alert increased prescribing by >5-fold among patients seen by high-volume cardiologists. Our findings support use of EHR alerts, especially in busy practice settings. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure [BETTER CARE-HF]; NCT05275920).

Bio(sensors) based on molecularly imprinted polymers and silica materials used for food safety and biomedical analysis: Recent trends and future prospects.

In recent decades, analytical techniques have increasingly focused on the precise quantification. Achieving this goal has been accomplished with conventional analytical approaches that typically require extensive pretreatment methods, significant reagent usage, and expensive instruments. The need for rapid, simple, and highly selective identification platforms has become increasingly pronounced. Molecularly imprinted polymer (MIP) has emerged as a promising avenue for developing advanced sensors that can potentially surpass the limitations of conventional detection methods. In recent years, the application of MIP-silica materials-based sensors has garnered significant attention owing to their distinctive characteristics. These types of probes hold a distinct advantage in their remarkable stability and durability, all of which provide a suitable sensing platform in severe environments. Moreover, the substrate composed of silica materials offers a vast surface area for binding, thereby facilitating the efficient detection of even minuscule concentrations of targets. As a result, sensors based on MIP-silica materials have the potential to be widely applied in various industries, including medical diagnosis, and food safety. In the present review, we have conducted an in-depth analysis of the latest research developments in the field of MIPs-silica materials based sensors, with a focus on succinctly summarizing and elucidating the most crucial findings. This is the first comprehensive review of integration MIPs with silica materials in electrochemical (EC) and optical probes for biomedical analysis and food safety.

Novel Note Templates to Enhance Signal and Reduce Noise in Medical Documentation: Prospective Improvement Study.

BACKGROUND: The introduction of electronic workflows has allowed for the flow of raw uncontextualized clinical data into medical documentation. As a result, many electronic notes have become replete of "noise" and deplete clinically significant "signals." There is an urgent need to develop and implement innovative approaches in electronic clinical documentation that improve note quality and reduce unnecessary bloating. OBJECTIVE: This study aims to describe the development and impact of a novel set of templates designed to change the flow of information in medical documentation. METHODS: This is a multihospital nonrandomized prospective improvement study conducted on the inpatient general internal medicine service across 3 hospital campuses at the New York University Langone Health System. A group of physician leaders representing each campus met biweekly for 6 months. The output of these meetings included (1) a conceptualization of the note bloat problem as a dysfunction in information flow, (2) a set of guiding principles for organizational documentation improvement, (3) the design and build of novel electronic templates that reduced the flow of extraneous information into provider notes by providing link outs to best practice data visualizations, and (4) a documentation improvement curriculum for inpatient medicine providers. Prior to go-live, pragmatic usability testing was performed with the new progress note template, and the overall user experience was measured using the System Usability Scale (SUS). Primary outcome measures after go-live include template utilization rate and note length in characters. RESULTS: In usability testing among 22 medicine providers, the new progress note template averaged a usability score of 90.6 out of 100 on the SUS. A total of 77% (17/22) of providers strongly agreed that the new template was easy to use, and 64% (14/22) strongly agreed that they would like to use the template frequently. In the 3 months after template implementation, general internal medicine providers wrote 67% (51,431/76,647) of all inpatient notes with the new templates. During this period, the organization saw a 46% (2768/6191), 47% (3505/7819), and 32% (3427/11,226) reduction in note length for general medicine progress notes, consults, and history and physical notes, respectively, when compared to a baseline measurement period prior to interventions. CONCLUSIONS: A bundled intervention that included the deployment of novel templates for inpatient general medicine providers significantly reduced average note length on the clinical service. Templates designed to reduce the flow of extraneous information into provider notes performed well during usability testing, and these templates were rapidly adopted across all hospital campuses. Further research is needed to assess the impact of novel templates on note quality, provider efficiency, and patient outcomes.

Cluster-Randomized Trial Comparing Ambulatory Decision Support Tools to Improve Heart Failure Care.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are underprescribed for patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study sought to compare effectiveness of 2 automated, electronic health record-embedded tools vs usual care on MRA prescribing in eligible patients with HFrEF. METHODS: BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) was a 3-arm, pragmatic, cluster-randomized trial comparing the effectiveness of an alert during individual patient encounters vs a message about multiple patients between encounters vs usual care on MRA prescribing. This study included adult patients with HFrEF, no active MRA prescription, no contraindication to MRAs, and an outpatient cardiologist in a large health system. Patients were cluster-randomized by cardiologist (60 per arm). RESULTS: The study included 2,211 patients (alert: 755, message: 812, usual care [control]: 644), with average age 72.2 years, average ejection fraction 33%, who were predominantly male (71.4%) and White (68.9%). New MRA prescribing occurred in 29.6% of patients in the alert arm, 15.6% in the message arm, and 11.7% in the control arm. The alert more than doubled MRA prescribing compared to usual care (relative risk: 2.53; 95% CI: 1.77-3.62; P < 0.0001) and improved MRA prescribing compared to the message (relative risk: 1.67; 95% CI: 1.21-2.29; P = 0.002). The number of patients with alert needed to result in an additional MRA prescription was 5.6. CONCLUSIONS: An automated, patient-specific, electronic health record-embedded alert increased MRA prescribing compared to both a message and usual care. These findings highlight the potential for electronic health record-embedded tools to substantially increase prescription of life-saving therapies for HFrEF. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations-Heart Failure [BETTER CARE-HF]; NCT05275920).

Leveraging clinical decision support tools to improve guideline-directed medical therapy in patients with atherosclerotic cardiovascular disease at hospital discharge.

BACKGROUND: Guidelines recommend moderate to high-intensity statins and antithrombotic agents in patients with atherosclerotic cardiovascular disease (ASCVD). However, guideline-directed medical therapy (GDMT) remains suboptimal. METHODS: In this quality initiative, best practice alerts (BPA) in the electronic health record (EHR) were utilized to alert providers to prescribe to GDMT upon hospital discharge in ASCVD patients. Rates of GDMT were compared for 5 months pre- and post-BPA implementation. Multivariable regression was used to identify predictors of GDMT. RESULTS: In 5985 pre- and 5568 post-BPA patients, the average age was 69.1 ± 12.8 years and 58.5% were male. There was a 4.0% increase in statin use from 67.3% to 71.3% and a 3.1% increase in antithrombotic use from 75.3% to 78.4% in the post-BPA cohort. CONCLUSIONS: This simple EHR-based initiative was associated with a modest increase in ASCVD patients being discharged on GDMT. Leveraging clinical decision support tools provides an opportunity to influence provider behavior and improve care for ASCVD patients, and warrants further investigation.

Systems biology under heat stress in Indian cattle.

Transcriptome profiling of Vrindavani and Tharparkar cattle (n = 5 each) revealed that more numbers of genes were dysregulated in Vrindavani than in Tharparkar. A contrast in gene expression was observed with 18.9 % of upregulated genes in Vrindavani downregulated in Tharparkar and 17.8% upregulated genes in Tharparkar downregulated in Vrindavani. Functional annotation of genes differentially expressed in Tharparkar and Vrindavani revealed that the systems biology in Tharparkar is moving towards counteracting the effects due to heat stress. Unlike Vrindavani, Tharparkar is not only endowed with higher expression of the scavengers (UBE2G1, UBE2S, and UBE2H) of misfolded proteins but also with protectors (VCP, Serp1, and CALR) of naïve unfolded proteins. Further, higher expression of the antioxidants in Tharparkar enables it to cope up with higher levels of free radicals generated as a result of heat stress. In this study, we found relevant genes dysregulated in Tharparkar in the direction that can counter heat stress.

Synthesis of eugenol derivatives and its anti-inflammatory activity against skin inflammation.

Eugenol is a phytochemical present in aromatic plants has generated considerable interest in the pharmaceutical industries mainly in cosmetics. A series of eugenol esters (ST1-ST7) and chloro eugenol (ST8) have been synthesized. The structures of newly synthesized compounds were confirmed by 1H and 13C NMR and mass spectrometry. In an effort to evaluate the pharmacological activity of eugenol derivatives, we explored its anti-inflammatory potential against skin inflammation using in-vitro and in-vivo bioassay. Synthesized derivatives significantly inhibited the production of pro-inflammatory cytokines against LPS-induced inflammation in macrophages. Among all derivatives, ST8 [Chloroeugenol (6-chloro, 2-methoxy-4-(prop-2-en-1-yl)-phenol)] exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the efficacy and safety in in-vivo condition. ST8 exhibited significant anti-inflammatory activity against TPA-induced skin inflammation without any skin irritation effect on experimental animals. These findings suggested that ST8 may be a useful therapeutic candidate for the treatment of skin inflammation.

Anti-psoriatic effect of Lavandula angustifolia essential oil and its major components linalool and linalyl acetate.

ETHNO-PHARMACOLOGICAL RELEVANCE: Lavender oil (LO) is an aromatic/essential oil extracted from Lavandula angustifolia and traditionally used as an aromatherapy massage oil due to its anti-inflammatory and wound healing property and also for providing the relief in other skin conditions such as psoriasis, dermatitis and eczema. However, LO has not been evaluated scientifically for psoriasis like skin inflammation. AIM OF THE STUDY: This study was aimed to investigate the LO and its major components linalool (L) and linalyl acetate (LA) against psoriasis like skin inflammation. MATERIALS AND METHODS: Anti-psoriatic activity was done using Imiquimod (IMQ) induced psoriasis like skin inflammation in BALB/c mice. Assessment of anti-psoriatic effect of LO, L and LA was done on the basis of change in ear thickness, psoriasis area severity index (PASI) scoring at alternative day, CosCam scoring using skin analyzer equipped with SkinSys software, biochemical, immunohistochemical and histological investigations. Level of effectiveness against psoriasis was investigated by percent reduction in PASI scores, CosCam scores and level of Th-1 and Th-17 cell expressing cytokines, as compared to the diseased mice. RESULTS: Topical application of LO 10% showed 73.67% recovery in PASI and 87% in Th-17 cell-specific cytokines towards normal as compared to disease group. L and LA were identified as the major components of LO and favoured ligands for selected psoriasis targets. At 2% topical dose, L and LA showed 64% and 47.61% recovery in PASI scores, respectively. Both, L and LA showed significant recovery in Th-1 specific TNF-α and IL-1ß however, only L showed significant recovery of Th-17 cytokines (IL-17 and IL-22). In contrast to LA (which restored granulosis), L restored epidermal hyperplasia and parakeratosis toward the normal condition. On the other hand, L also reduced the expression of NF-κß, ccr6 and IL-17, while LA reduced the expression of NF-κß only. At 10% topical dose, LO was observed to be slight irritant while at 2% topical dose, L and LA were found non-irritant to the skin. CONCLUSION: This study proves the effectiveness of LO and its major phytoconstituents linalool and linalyl acetate against IMQ induced psoriasis like skin inflammation and provides the scientific evidence for topical use of lavender oil.

COVID-19 - Recent advancements in identifying novel vaccine candidates and current status of upcoming SARS-CoV-2 vaccines.

The COVID-19 pandemic caused by SARS-CoV-2 has spread rapidly. To date, countries have relied on the prevention of the disease through isolation, quarantine, and clinical care of affected individuals. However, studies on the roles of asymptomatic and mildly infected subjects in disease transmission, use of antiviral drugs, and vaccination of the general population will be very important for mitigating the effects of the eventual return of this pandemic. Initial investigations are ongoing to evaluate antigenic structures of SARS-CoV-2 and the immunogenicity of vaccine candidates. There also is a need to comprehensively compile the details of previous studies on SARS-related vaccines that can be extrapolated to identify potent vaccine targets for developing COVID-19 vaccines. This review aims to analyze previous studies, current status, and future possibilities for producing SARS-CoV-2 vaccines.

In vitro and in vivo immunomodulatory potential of Pedicularis longiflora and Allium carolinianum in alloxan-induced diabetes in rats.

Pedicularis longiflora Rudolph (Orobanchaceae) and Allium carolinianum Linn (Alliaceae) are two important medicinal plants found in trans-Himalayan Changthang. The immunomodulatory potential of these plants has not been explored. In the present study, we evaluated the in vitro and in vivo immunomodulatory potential of P. longiflora and A. carolinianum in alloxan-induced diabetes in Wistar rats. The ethanol extracts of the aerial parts of P. longiflora and whole plant parts of A. carolinianum were used for studying the in vitro immunomodulatory activity using lymphocyte stimulation and cytokine release assays. For the in vivo study, 5 groups of 6 rats per group, including alloxan-induced diabetic and plant extract-treated rats, were evaluated for cell-mediated immune (CMI) and humoral immune (HMI) responses in a 42-day experimental trial using doses of 500mg/kg b.wt. for P. longiflora and 250mg/kgbwt. for A. carolinianum. For P. longiflora, the median effective dose was found to be 500mg/kg. The in vitro lymphocyte stimulation index for P. longiflora was significantly higher (1.73±0.04, p<0.05) than that for A. carolinianum (1.27±0.06). However, the release of transforming growth factor-ß1 (TGF-ß1, 15.63±1.00, p<0.05) by P. longiflora was significantly lower than that by A. carolinianum (21.61±1.19), suggesting a better immune response by P. longiflora than by A. carolinianum. P. longiflora significantly increased the ear thickness (53.12%), inflammatory cellular infiltration (200.00±11.42), and total leukocyte count (7.44±0.02) compared to A. carolinianum (47.57%, 165.83±3.96, and 7.01±0.01, respectively). P. longiflora significantly reduced the percentage of leukocytes with depolarized mitochondria (3.24±0.16%) and apoptosis (1.81±0.07%), and induced a better CMI response than A. carolinianum. Significantly (p<0.05) higher hemagglutination titer (28.37±0.80) and IgG production (6.43±0.34mg/mL) were observed in the P. longiflora-treated group than in the A. carolinianum-treated group (23.93±0.58 and 6.23±0.37mg/mL). Plasma tumor necrosis factor-α (TNF-α) and TGF-ß1 levels, and nuclear factor-κB (NF-κB) expression were significantly (p<0.05) lower in the P. longiflora-treated group than in the A. carolinianum-treated group. This may be due to better HMI responses produced by P. longiflora than by A. carolinianum. This is the first study to show that P. longiflora ethanol extract has more potent in vitro and in vivo immunomodulatory activities than A. carolinianum, especially in alloxan-induced diabetic rats. However, further research is needed to identify the different molecular mechanisms involved in mediating this immunomodulatory response.

Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders - A Review.

BACKGROUND: Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases. OBJECTIVE: To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patients regardless of their background on equality basis. RESULTS: Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogenactivated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common antiinflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppresants used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration. CONCLUSION: Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.

Fraxetin and ethyl acetate extract from Lawsonia inermis L. ameliorate oxidative stress in P. berghei infected mice by augmenting antioxidant defence system.

BACKGROUND: Lawsonia inermis L. is a well-documented plant for cosmetic as well as medicinal properties. It is used by local communities in India and Nigeria for the treatment of many parasitic diseases, including malaria. HYPOTHESIS/PURPOSE: Earlier studies on the plant's antiplasmodial activity were not assigned to any phytochemical with no quality assurance data. In this report, a recent chemically characterized extract and it's major constituent were investigated for in vitro antiplasmodial activity on chloroquine sensitive NF-54 strain. Furtherly, the potent extract and this constituent were assessed in vivo in Plasmodium berghei infected mice. The bioactive phytochemical and enriched extract were also monitored against various oxidative stress parameters. STUDY DESIGN/METHOD: The extract characterization was done by the quantitative analysis of eight phytochemicals using gradient reverse phase HPLC method. In vitro antiplasmodial activity was evaluated on chloroquine sensitive NF-54 strain by the determination of pfLDH activity. In vivo activity of the most potent extract and constituent were evaluated in P. berghei infected mice upon oral administration. The estimation of oxidative stress was done by monitoring various enzymatic and non-enzymatic parameters. RESULTS: The ethyl acetate extract of leaves (IC50 9.00 ±â€¯0.68 µg/ml) and fraxetin (IC50 19.21 ±â€¯1.04 µM) were the most effective in in vitro assays therefore selected for in vivo tests. The administration of the ethyl acetate extract of leaves and fraxetin to the infected mice resulted in significant (p < .05) suppression of parasitaemia as evidenced by a 70.44 ±â€¯2.58% to 78.77 ±â€¯3.43% reduction compared to non-infected group. In addition, a two-fold increase in mean survival time, a significant (p < .05) reduction in lipid peroxidation and an elevation in glutathione, catalase and superoxide dismutase were also observed in treated mice. The post-infection treatment also led to an augmentation of endogenous antioxidant enzymes (GST, GR, GPx) with respect to the infected control. A significant (p < .05) elevation in serum Nrf2-antioxidant response element level responsible for the activation of endogenous enzymes was also observed. CONCLUSION: It was evident from the experiments that ethyl acetate extract of L. inermis and fraxetin were able to suppress the oxidative damage by augmenting endogenous antioxidant system and thus ameliorated the plasmodium infection in mice.