Inulin: Unveiling its potential as a multifaceted biopolymer in prebiotics, drug delivery, and therapeutics.

In recent years, inulin has gained much attention as a promising multifunctional natural biopolymer with numerous applications in drug delivery, prebiotics, and therapeutics. It reveals a multifaceted biopolymer with transformative implications by elucidating the intricate interplay between inulin and the host, microbiome, and therapeutic agents. Their flexible structure, exceptional targetability, biocompatibility, inherent ability to control release behavior, tunable degradation kinetics, and protective ability make them outstanding carriers in healthcare and biomedicine. USFDA has approved Inulin as a nutritional dietary supplement for infants. The possible applications of inulin in biomedicine research inspired by nature are presented. The therapeutic potential of inulin goes beyond its role in prebiotics and drug delivery. Recently, significant research efforts have been made towards inulin's anti-inflammatory, antioxidant, and immunomodulatory properties for their potential applications in treating various chronic diseases. Moreover, its ability to reduce inflammation and modulate immune responses opens new avenues for treating conditions such as autoimmune disorders and gastrointestinal ailments. This review will attempt to illustrate the inulin's numerous and interconnected roles, shedding light on its critical contributions to the advancement of healthcare and biomedicine and its recent advancement in therapeutics, and conclude by taking valuable insights into the prospects and opportunities of inulin.

Calcium phosphate nanoparticles conjugated with outer membrane vesicle of Riemerella anatipestifer for vaccine development in ducklings.

Biodegradable calcium phosphate nanoparticles offer a viable substitute for traditional adjuvants such as aluminum in vaccine production. Calcium phosphate nanoparticle adjuvanted with outer membrane vesicle (OMV) of gram negative bacteria may induce efficient immune response in the host. The present study was carried out to evaluate the potential of a mucosal vaccine formulation of calcium phosphate (CAP) nanoparticle using OMV of Riemerella anatipestifer (RA) as antigen against New Duck disease in ducks. The work was initiated with isolation, identification of RA, followed by OMV production and extraction. The CAP-OMV nanoparticle was prepared and characterized. The efficacy of the vaccine formulation and toxicity were studied in ducks. The average OMV yield in terms of protein concentration was found to be 122.33 ± 3.48 mg per liter of BHI broth. In SDS-PAGE, isolated OMVs exhibited presence of 16 distinct protein bands with molecular weight ranging from 142.1 to 12.1 kDa. Seven protein bands of 74.1, 69.3, 55.5, 50.6, 45.6, 25.1 and 13.1 kDa were detected relatively more distinct. The major bands detected in our findings were 42 kDa, 37 kDa and 16 kDa that corresponds to OmpA, OmpH, P6 respectively. The mean zeta size (±SD) and potential of the nanoparticle were 246.20 ± 0.53 nm and -25.60 ± 5.97 respectively. In transmission electron microscopy (TEM), the nanoparticles exhibited an average diameter of 129.80 ± 11.10 nm and displayed spherical morphology. The median protective dose (PD50) of CAP-OMV nanoparticle was 1881.10 µg of protein. Group I ducks received 3762 µg of protein (entrapped protein in CAP-OMV nanoparticle) via intra nasal route and it showed the highest serum IgG and secretory IgA level than other immunized groups. All experimental ducks were challenged with 10 × LD50 on 35 days of post primary immunization. Group I showed 100 % survivability in the challenge study. No gross and biochemical indication of acute or chronic toxicity were recorded. In conclusion, our results suggest that CAP-OMV nanoparticle can be a safe and efficient mucosal vaccine delivery system for RA, eliciting strong immune response in the host.

Incidence of diabetes mellitus in patients treated with immune checkpoint inhibitors (ICI) therapy - A comprehensive cancer center experience.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and more patients are receiving ICIs than before. Although this has improved cancer care but so has the increase in the incidence of immune-related adverse events (irAEs) including endocrinopathies. ICI-induced diabetes mellitus (DM) is a rare irAE with an approximate incidence of 1%. Due to paucity of data in literature about ICI-induced DM, we conducted a study to report the incidence and characteristics of new onset and worsening of DM in patients treated with ICIs. METHODS: We conducted a retrospective review of patients who received ICIs during 10-year period. We identified patients with newly diagnosed DM and worsening of preexisting DM. FINDINGS: Among 2,477 patients who received one or multiple ICIs, 14 patients developed new onset DM and 11 patients experienced worsening of pre-existing DM. Median time to new onset or worsening DM from ICI treatment initiation was âˆ¼ 12 weeks. Median hemoglobin A1c was 6.2% at baseline and 8.5% at the onset of ICI-induced DM. Seven patients presented with diabetes ketoacidosis (DKA), all in the new onset group. (p = 0.02) No significant difference was observed between two groups regarding personal history of autoimmune disorder or family history of DM. (p greater than 0.05) Positive autoantibodies were found in three patients [two with Glutamic Acid Decarboxylase (GAD65) antibodies and one with insulin autoantibodies (IAA)]. INTERPRETATION: The incidence of new onset and worsening DM in patients treated with ICIs was 1.01%.

A Comprehensive Review on Pharmacologically Active Phyto-Constituents from Hedychium species.

In this review, we describe and discuss the phytoconstituents present in Hedychium species and emphasize their potential as drug candidates. Though they are widely validated in vitro and in vivo models, to date, no efforts have been made to compile in a single review all the pharmacologically active phytoconstituents from Hedychium species, and their pharmacological and toxicity profile. In this study, we present a reinvestigation of the chemical constituents present in Hedychium species obtained from the essential oil and solvent extraction of the flowers, leaves and rhizomes under consideration. Key databases such as PubMed, Science Direct, Scopus, and Google Scholar amongst others were probed for a systematic search using keywords to retrieve relevant publications on this plant. An exhaustive electronic survey of the related literature on Hedychium species resulted in around 200 articles. Articles published between the years 1975-2021 were included. The studies conducted on either crude extracts, solvent fractions or isolated pure compounds from Hedychium species reported with a varied range of biological effects such as anti-inflammatory, analgesic, antidiabetic, potentially anti-asthmatic, and cytotoxic, among other related activities of the chemical constituents present in its essential oil and solvent extract deployed in this review. Traditional and herbal medication around the world that uses different parts of Hedychium species were considered for anti-inflammatory, skincare, analgesic, anti-asthmatic, anti-diabetic, antidotal uses, among others. These uses support the idea that chemical constituents obtained from solvent extraction may also exert the same action individually or in a synergistic manner. The review concluded that there is scope for computation and biological study to find out possible new targets for strengthening the potency and selectivity of the relevant compounds, and to find a commercial method for extraction of active pharmaceutical ingredients.

HYPOTHYROIDISM AND GOITER IN A YOUNG MALE WITH SUSPECTED DIETARY IODINE DEFICIENCY FOLLOWED BY THYROTOXICOSIS AFTER IODINE SUPPLEMENTATION.

OBJECTIVE: Iodine deficiency disorders (IDDs) remain a major public health concern in most parts of the world but are extremely rare in North America. We describe a case of goiter in a young male with dietary history and findings suggestive of IDD. METHODS: Laboratory and imaging procedures including thyroid function tests, autoantibodies, urine iodine, thyroid ultrasound, and radioactive iodine (RAI) uptake scan were performed. RESULTS: On initial presentation, thyroid-stimulating hormone (TSH) was 24.4 mIU/L (normal range is 0.4 to 5.0 mIU/L), free thyroxine was <0.4 ng/dL (normal range is 0.8 to 1.8 ng/dL), and thyroid peroxidase antibody was positive at 43 IU/mL (normal range is <35 IU/mL). He reported consuming strawberries and peanut butter sandwiches with no intake of dairy or seafood due to gastrointestinal issues (abdominal pain, bloating, and nausea). Physical exam revealed a diffusely enlarged, palpable thyroid gland (grade II goiter). Ultrasound of the neck showed an enlarged thyroid gland with no nodules. RAI uptake scan showed diffuse increased uptake (91%). Given his poor diet, a 24-hour urinary iodine excretion test was ordered which was suggestive of very low iodine intake. He was started on multivitamins with 150 µg of iodine daily. On follow up, clinical exam showed grade I goiter and TSH had normalized to 0.7 mIU/L and free thyroxine was 1.2 ng/dL. He continued on iodine supplementation and tolerated iodine-rich foods. Six months later, thyroid function tests showed hyperthyroidism with TSH of <0.002 ng/dL and free thyroxine was elevated to 2.8 ng/dL. Iodine supplements were stopped. CONCLUSION: Hypothyroidism and goiter due to IDD should be suspected in the setting of poor dietary intake. IDDs can be rapidly diagnosed in a patient on a restricted diet with multiple urinary iodine determinations and RAI study. Regular thyroid labs should be done to monitor for hyperthyroidism that can develop after iodine supplementation.

Phenolic rich Cocos nucifera inflorescence extract ameliorates inflammatory responses in LPS-stimulated RAW264.7 macrophages and toxin-induced murine models.

Anti-inflammatory and antinociceptive effects of the acetone extract of Cocos nucifera (CnAE), an important ingredient in several traditional drugs, have been studied using different in vitro and in vivo models. CnAE did not show any observable toxicity in RAW264.7 macrophages by MTT assay. The calorimetric analysis (total COX, 5-LOX, MPO, iNOS and NO), ELISA (IL-1ß, IL-6, TNF-α and PGE2) and qRT-PCR (IL-1ß, IL-6, TNF-α and NF-κB) were performed in LPS-induced RAW264.7 macrophages. Phosphorylation of NF-κBp65 and IκB was determined by western blotting. CnAE (100 µg/mL) remarkably inhibited total COX (68.67%) and 5-LOX (63.67%) activities, and subsequent release of iNOS, NO and PGE2 (p ≤ 0.05) in RAW264.7 cells treated with LPS. ELISA showed CnAE markedly decreased the level of pro-inflammatory cytokines IL-1ß (p ≤ 0.001), IL-6 (p ≤ 0.001) and TNF-α (p ≤ 0.001) in LPS treated RAW264.7 cells. CnAE (100 µg/mL) also significantly down-regulated the mRNA expressions of pro-inflammatory cytokines (IL-1ß, p ≤ 0.05; IL-6, p ≤ 0.01 and TNF-α, p ≤ 0.001) and NF-κB (p ≤ 0.001) against LPS-induction. Moreover, LPS-induced phosphorylation of IκB-α and NF-κB p65 was significantly inhibited by CnAE (100 µg/mL). In vivo anti-inflammatory studies showed that CnAE (400 mg/kg) significantly inhibited carrageenan-induced acute paw oedema (59.81%, p ≤ 0.001) and formalin-induced chronic paw oedema (52.90%, p ≤ 0.001) in mice. CnAE at a dose of 400 mg/kg also showed a significant anti-nociceptive effect on acetic acid-induced writhing (48.21%, p ≤ 0.001) and Eddy's hot plate methods. These findings suggest that CnAE has significant anti-inflammatory and anti-nociceptive properties, mainly attributed to the inhibition of NF-κB/IκB signalling cascade.

Regulatory Requirements for Quality Control of Unani Medicines.

Compliance with pharmacopeial standards is mandatory to ensure the quality, safety, and efficacy of medicines. In India, allopathy, Ayurveda, Siddha, Unani, and homeopathy are the recognized systems of medicine and come under the provisions of different regulations. Promulgation of the "Drugs and Cosmetics Act, 1940" and the rules thereunder provide a regulatory framework for medicines of all of these systems and also prescribe "Pharmacopoeia and Formularies" for regulatory quality standards. Unlike in many other countries, the Act prescribes independent pharmacopeias for each system of medicine. The Unani Pharmacopoeia of India (UPI) and the National Formulary of Unani Medicine are the regulatory compendia for quality standards and manufacturing of Unani medicines, respectively. The Pharmacopoeia consists of Part I (single drugs) and Part II (formulations). Unani medicines are presented as classical or patent and proprietary formulations prepared using single ingredients or multiple ingredients of plant, animal, mineral, and/or metal origin. UPI Part I is published in six volumes comprising 298 monographs on Unani drugs derived from plants (single drugs). Part II is published in three volumes encompassing formulations, standard operating procedures, and quality standards for 150 classical formulations of Unani medicines, which are chosen from the National Formularies of Unani Medicine. The National Formulary of Unani Medicine is published in six parts comprising 1229 formulations of Unani medicines. Each monograph of the Pharmacopoeia provides specific analytical parameters and limits (standards) to ensure the quality of drugs or medicines. This communication reviews the UPI, the National Formulary of Unani Medicine, regulatory quality standards (parameters), and analytical techniques adopted for pharmacopeial standards of Unani drugs and medicines.

Comparative evaluation of hypoglycemic and hypolipidemic activity of various extract of Anogeissus latifolia bark in streptozotocin-induced diabetic rats.

Background Anogeissus latifolia Wall. (A. latifolia) bark has been traditionally used in the treatment of various diseases which includes diabetes and general debility. The present study was aimed to investigate the comparative hypoglycemic and hypolipidemic activity of various extracts of A. latifolia bark in streptozotocin-induced type 1 diabetic rats. Methods Acute toxicity was carried out at 2 g/kg dose of petroleum ether extract of A. latifolia bark (PEALB), chloroform extract of A. latifolia bark (CEALB) and methanol extract of A. latifolia bark (MEALB) in rats. Diabetes was induced by streptozotocin (STZ, 60 mg/kg, i.p.) and it was confirmed at 72 h. Diabetic rats received above extracts at 100 and 200 mg/kg doses for 28 days. Body weight and blood glucose level were determined at every week after the treatment schedule. Serum biochemical parameters and lipid profile levels were estimated at the end of the study. Results PEALB, CEALB and MEALB were non-toxic and no death was observed at 2 g/kg dose. Administration of MEALB at 100 and 200 mg/kg showed significant (p< 0.01, p< 0.05) improvement in body weight and reduction in blood glucose at third and fourth week of treatment. Altered serum biochemical parameters and lipid profiles level were brought to near normal level significantly (p<0.001) compared to diabetic control rats after the administration of both doses of MEALB. However, PEALB and CEALB did not exhibit significant hypoglycemic and hypolipidemic activity. Conclusions Our findings revealed that long-term (28 days) treatment of MEALB possesses significant hypoglycemic and hypolipidemic activity compared to PEALB and CEALB in type 1 diabetic rats and given evidence to the traditional use of A. latifolia bark in diabetes.

Comparison of efficacy of alternative medicine with allopathy in treatment of oral fungal infection.

This clinical study assessed and compared the efficacy of tea tree oil (TTO), an alternative form of medicine, with clotrimazole (i.e., allopathy) and a conservative form of management in the treatment of oral fungal infection. In this interventional, observational, and comparative study, we enrolled 36 medically fit individuals of both sexes who were aged 20-60 years old. The participants were randomly assigned to three groups. Group I was given TTO (0.25% rinse) as medicament, Group II was given clotrimazole, and Group III was managed with conservative treatment. The results were analyzed from the clinical evaluation of lesions, changes in four most common clinical parameters of lesions, and subjective symptoms on periodic follow-up. Based on the results, the percentage efficiency of the two groups were taken and compared through a bar graph on the scale of 1. No toxicity to TTO was reported. Group I (TTO) was found to be more efficient than the other two groups, as changes in four parameter indices of lesions were noted, and results for all three groups were compared on a percentage basis. The study concluded that TTO, being a natural product, is a better nontoxic modality compared to clotrimazole, in the treatment of oral fungal infection and has a promising future for its potential application in oral health products.

Antimicrobial biosynthetic potential and genetic diversity of endophytic actinomycetes associated with medicinal plants.

Endophytic actinomycetes are one of the primary groups that share symbiotic relationships with medicinal plants and are key reservoir of biologically active compounds. In this study, six selective medicinal plants were targeted for the first time for endophytic actinomycetes isolation from Gibbon Wild Life Sanctuary, Assam, India, during winter and summer and 76 isolates were obtained. The isolates were found to be prevalent in roots followed by stem and leaves. 16S rRNA gene sequence analysis revealed 16 genera, including rare genera, Verrucosispora, Isoptericola and Kytococcus, which have never been previously reported as endophytic. The genus Streptomyces (66%) was dominant in both seasons. Shannon's diversity index showed that Azadirachta indica (1.49), Rauwolfia serpentina (1.43) and Emblica officinalis (1.24) were relatively good habitat for endophytic actinomycetes. Antimicrobial strains showed prevalence of polyketide synthase (PKS) type-II (85%) followed by PKS type-I (14%) encoded in the genomes. Expression studies showed 12-fold upregulation of PKSII gene in seventh day of incubation for Streptomyces antibioticus (EAAG90). Our results emphasize that the actinomycetes assemblages within plant tissue exhibited biosynthetic systems encoding for important biologically active compounds.

Comparative study of effect of anuloma-viloma (pranayam) and yogic asanas in premenstrual syndrome.

The present study was planned to investigate the effects of Anuloma-viloma and specific yogic asanas in Premenstrual syndrome (PMS). The study group comprised of 60 females suffering from PMS between the age group of 18- 40 years, having 28-34 days regular menstrual cycle, further subdivided into 3 groups having equal number (n = 20) of subjects-group A (no intervention), group B (Anuloma-viloma) and group C (yogic asanas). Age-matched 30 healthy female subjects were taken as control. In all the subjects, a baseline recording of the systolic (SBP) and diastolic blood pressure (DBP) from the right arm was taken using an automated sphygmomanometer. The heart rate (HR/min), electromyogram (EMG; mV), galvanic skin response (GSR; komega), respiratory rate (RR/min), peripheral temperature (T; degrees F), were recorded simultaneously, on an automated biofeedback apparatus Relax 701. The subjects of group A and group B performed yogic exercises, regularly for 7 days prior to the expected date of menstruation for 3 consecutive menstrual cycles. The parameters were recorded again at the end of 7 days in each menstrual cycle. We observed that, in the group A and group B, HR, SBP, DBP, EMG, GSR and RR showed a very significant reduction (P < 0.001) and T rose more significantly (P < 0.001) after the 3rd menstrual cycle, when compared with their basal levels. On computing the percentage difference between the baseline and post values in all the three groups and than comparing this percentage difference, we found a y significant difference (P < 0.05) between the groups. In the present study, the relaxation response in the females suffering from PMS showed a reduction in an abnormally high basal sympathetic activity and a heightened relaxation response in both the study groups (group B and Group C) in comparison with group A.

Rodenticide poisoning as a cause of quadriparesis: a rare entity.

Acute flaccid paralysis with its wide repertoire of causes presents a challenge to the clinician. We present a case of barium carbonate poisoning, a rare yet easily treatable cause of acute quadriparesis. Barium acts by redistribution of potassium from the extra- to intravascular compartment causing hypokalemia. Early recognition and prompt potassium supplementation under cardiac monitoring yield gratifying results.

Should trichrome stain be used on all post-liver transplant biopsies with hepatitis C virus infection to estimate the fibrosis score?

Recurrent hepatitis C is virtually universal after liver transplantation; however, an individual patient's clinical course and disease burden are highly variable and difficult to predict. The fibrosis score determined on posttransplant biopsies appears to be a sensitive and specific marker of disease progression and severity. Currently, the fibrosis score is determined from hematoxylin and eosin (H&E)-stained tissue sections supplemented by variable use of trichrome stain or other connective tissue-specific stains. In this study, we compare the fibrosis score on H&E stain with that obtained with trichrome stain in posttransplant liver biopsies of patients with hepatitis C. A total of 197 liver biopsies from 105 allograft patients with hepatitis C were reviewed. The mean fibrosis stage was 1.0 +/- 1.25 with H&E stain versus 1.69 +/- 1.42 with trichrome stain (P < 0.00001). The trichrome staging score was higher in 53.3%, lower in 3%, and the same in 43.7%. The fibrosis stage was raised by 2 or more points in 17.8% and elevated into a bridging category in 14.7%. No significant differences in clinical and laboratory levels were measured in patients with higher fibrosis scores. In conclusion, the hepatic fibrosis score is significantly underestimated by H&E stain in the posttransplant setting in patients with hepatitis C. The fibrosis stage may be an indicator of significant liver damage in these patients. Accuracy of its determination may be most easily facilitated by employment of a connective tissue stain.

Distillery effluent effect on seed germination, early seedling growth and pigment content of sugarbeet (Beta vulgaris Linn. var. mezzanau-poly).

Bioassay studies were carried out to assess the toxicity of distillery effluent on seed germination, seedling growth and pigment contents. Higher concentrations (> 5%) of effluent were found to be toxic but however, can be used for irrigational purpose after proper dilution.