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Abstract: Proteins and peptides possess considerable potential in treating solid tumors because of their unique properties. At present, there are over 100 peptide-based formulations on the market. Today, peptides and proteins are in more demand due to their selective nature and high target-binding efficiency. Targeting solid tumors with compounds of molecular weight less than 10 kDa are much more desirable because they undergo excessive penetration in view of the fact that they are small sized. The solid tumors have thick tissues and possess excessive interstitial fluid pressure, because of which high molecular compounds cannot enter. The properties of proteins and peptides induce low toxic effects and lessen the major side effects caused by chemical-based drugs. However, their delivery is quite challenging as most proteins and peptides stop functioning therapeutically when following a parenteral route of administration. This paper elaborates on the importance of new age formulations of peptides and proteins followed by their recently documented advancements that increase their stability and delay their metabolism, which helps to target solid tumors.

Publisher Copyright: © 2022 by the authors. As acetylcholinesterase (AChE) plays a crucial role in advancing Alzheimer’s disease (AD), its inhibition is a promising approach for treating AD. Sulindac is an NSAID of the aryl alkanoic acid class, consisting of a indene moiety, which showed neuroprotective behavior in recent studies. In this study, newer Indene analogs were synthesized and evaluated for their in vitro AChE inhibition. Additionally, compared with donepezil as the standard drug, these Indene analogs were accessed for their cell line-based toxicity study on SH-SY5Y cell line. The molecule SD-30, having hydrogen bond donor (HBD) at para-position, showed maximum AChE inhibition potential (IC50 13.86 ± 0.163 µM) in the indene series. Further, the SD-30 showed maximum BuChE inhibition potential (IC50 = 48.55 ± 0.136 µM) with a selectivity ratio of 3.50 and reasonable antioxidant properties compared to ascorbic acid (using DPPH assay). SD-30 (at a dose level: of 10 µM, 20 µM) effectively inhibited AChE-induced Aβ aggregation and showed no significant toxicity up to 30 mM against SH-SY5Y cell lines.

Background: The burden of Chronic Respiratory disease including chronic obstructive pulmonary disease to patients, their caretakers, and health system is gradually increasing. COPD is also associated with the morbidity, mortality, disability adjusted life years and highest costs. Digital health interventions for the self-management of COPD exacerbations could improve the positive outcomes for COPD patients. Aim: This systematic review will be conducted with the aim of creating an evidence base for digital health intervention for the self-management of COPD. Method: The searches will be carried out in six databases: PubMed, Scopus, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science, CINAHL, and ProQuest between 2005 to 2021. Studies assessing the impact of digital health intervention for the self-management of COPD published in English language will be included. WHO’s Monitoring and Evaluating Digital Health intervention stages maturity life cycle will be used to assess the implementation approach of included studies. Critical appraisal of the included studies will be conducted using Joanna Briggs institute critical appraisal tool.Discussion: The findings of this review will be utilized to inform the designing of informatics platform for the self-management of COPD in India.

A practical copper-catalyzed, 2-picolinamide-directed ortho C–H amination of anilines with benzoyl-protected hydroxylamines has been disclosed that proceeds smoothly without any external stoichiome...

Objectives: Musculoskeletal diseases, or MSDs, are injuries and illnesses that affect the musculoskeletal system or how the human body moves. Diabetes mellitus and several musculoskeletal disorders (MS) are connected (DM). Examining the connection between musculoskeletal issues and diabetes mellitus in diabetic patients is the goal of this study. Methods: Patients with diabetes mellitus were included in a cross-sectional study. Both the patients' demographic data and the DM features were noted. Clinical tests and research were used to evaluate musculoskeletal and vascular diseases. The factor correlations of MS illnesses were assessed using both univariate and multivariate analysis. Results: A total of 308 individuals were included, of whom 84.5 percent had type 2 diabetes and 15.5 percent had type 1 diabetes. Twenty-five percent of the patients had osteoarthritis. Duputrens contracture was detected in 1.29 percent of cases, Carpel tunnel syndrome in 9.0 percent, and reduced joint mobility in 4.22 percent of cases. In 15.5 percent of cases, shoulder capsulitis was detected. Increased prevalence of hand anomalies was linked to long-term diabetes and dyslipidemia. Conclusions: Numerous elements of diabetes have been connected to musculoskeletal disorders. Haemoglobin A1c levels do not appear to be related to the onset of musculoskeletal disorders.

A practical copper-catalyzed, 2-picolinamide-directed ortho C-H amination of anilines with benzoyl-protected hydroxylamines has been disclosed that proceeds smoothly without any external stoichiometric oxidant or additives. Remarkably, besides anilines, bicyclic naphthyl or heterocyclic amines furnished amination products with five- and six-membered cyclic and acyclic amines at the ortho position selectively. This electrophilic C-H amination also proceeds smoothly in water under slightly modified reaction conditions.

In this study, metabolic stability and biological evaluation of 99mTc labelled 6-hydrazinopyridine-3-carboxylic-acid (HYNIC)-Tyr3-Octreotide was reported as a candidate for imaging somatostatin-receptor (SSTR)-positive tumors. The metabolic stability analysis did not show any evidence of breaking of the labeled compound and formation of free 99mTc. In biodistribution and scintigraphy imaging study, radiopeptide have showed high and receptor-specific uptake in the SSTR2 positive organs, tumor with rapid renal excretion from non-target tissues, illustrating the excellent properties of this agent for SSTR tumor imaging.

99mTc-paclitaxel was synthesized by using sodium borohydride as a reducing agent. Greater than 95 % labelling efficiency was achieved. Radiochemical purity of the synthesized 99mTc-paclitaxel was validated by thin layer chromatography (TLC) scanner and high performance liquid chromatography (HPLC). 99mTc-paclitaxel passed in vitro stability tests. Biodistribution and scintigraphy studies were performed in Sprague–Dawley rats. The biodistribution study results of 99mTc-paclitaxel were related mainly to the metabolism and excretion routes followed by the parental drug, paclitaxel. Apart from that, biodistribution of 99mTc-paclitaxel was altered after pre-treatment with cold paclitaxel. Hence, 99mTc-paclitaxel may be used as a tracer for paclitaxel.

AIM: Finding the prevalence of hypothyroidism in PCOS and to determine the association between hypothyroidism and various clinical and laboratory parameters in PCOS. SETTING: The study was conducted as a prospective observational study on 196 USG diagnosed cases of PCOS who attended the outpatient wing of MKCG Medical College Hospital, Berhampur, Odisha, India. METHODS: All the USG proven cases of PCOS were subjected to investigations like FSH, LH, FBS, PPBS, Serum Insulin, TSH, Free T3, Free T4. After an overnight fasting, basal venous blood sample was taken. TFT including TSH, Free T3 and Free T4 was estimated using chemiluminescence method. According to this, TSH normal range was taken as 0.34-4.25 µIU/ml, Free T3 normal range was 2.4-4.2 pg/ml, Free T4 normal range was 0.8-1.7 ng/dl 137 . TSH above 4.25 µIU/ml, Free T3 below 2.4 pg/ml and Free T4below 0.8 ng/dl was considered as overt hypothyroidism and high TSH with normal Free T3 and Free T4 are considered as subclinical hypothyroidism. RESULTS: The mean age of presentation was 27.28± 10.56 years. 78.57% of cases had menstrual complaints. 20.40 % 0f cases had Secondary Amenorrhoea, 56.12 % had Oligomenorrhoea, 2.04 % had Polymenorrhoea and 21.42% had normal menstrual cycles. 76.53 % of cases had Hyperandrogenism. 66.32 % had hirsuitism, out of which 69.23 % had mild hirsuitism, 29.23 % had moderate hirsuitism and 1.53 % had severe hirsuitism. 31.63% of cases had Acne.70 % of married cases had Infertility. Out of that 79.59 % had primary infertility and 20.40 % had secondary infertility. 38.77 % had infertility of duration 1-2 years, 51.02 % had infertility of 3-5 years and 10.20 % had infertility of >5 years. 64.28 % of cases had increased BMI (≥25 kg/m 2 ). The prevalence of hypothyroidism in PCOS was 13.26 %. Out of that 57.69 % had subclinical hypothyroidism and 42.30 % had overt hypothyroidism. 96.15 % of PCOS with hypothyroidism had menstrual irregularities like oligomenorrhoea and secondary Amenorrhoea. This association was found to be statistically significant. 96.15 % of PCOS with hypothyroidism had features of hyperandrogenism like acne and hirsuitism. This association was found to be statistically significant.84.61 % of PCOS with hypothyroidism had increased BMI (≥25 kg/m 2 .) This association was found to be statistically significant. PCOS and Hypothyroidism are closely related. CONCLUSION: There is increased prevalence of hypothyroidism in PCOS. The relationship between thyroid profile and PCOS is being tried to be explored more and thus the problems of PCOS can be solved to some more extent.

AIM: This study was designed to define diagnostic value of hysteroscopy in perimenopausal abnormal uterine bleeding compared to histopathology study of blind dilatation & curettage. SETTING: The study entitled "Diagnostic Value of Hysteroscopy in Perimenopausal Abnormal Uterine Bleeding Compared to Histopathology Study of Blind Dilatation & Curettage" was done in M.K.C.G. Medical College & Hospital, Berhampur, Odisha, India. The study period extended from August 2012 to August 2013. METHODS: 100 patients in perimenopausal age group with abnormal uterine bleeding underwent hysteroscopy under short general anaesthesia followed by blind D&C. The findings of hysteroscopy were compared with histopathology study of D&C. RESULTS: In the present series overall Diagnostic accuracy, Sensitivity, Specificity, Positive predictive value, Negative predictive value of hysteroscopy are 90.2%, 85.11%, 98.06%, 90.28%, 94.69% respectively. Sensitivity, Specificity, Positive predictive value, negative predictive value of hysteroscopy for submucous myoma was 100% each. Sensitivity, Specificity, Positive predictive value, Negative predictive value of hysteroscopy for endometrial polyp was 100, 97.61, 88.88, 100% respectively. CONCLUSION: Hysteroscopy is a valuable, simple, low-risk technique which allows an adequate exploration of uterine cavity under visual control. It ensures speed and safety with the diagnosis and treatment. The results are immediately available. It allows finding out the source of bleeding and perform a directed biopsy from the suspected area. Hysteroscopic-guided biopsy and histopathology are considered as the "new gold standard" in evaluating a case of perimenopausal abnormal uterine bleeding.

Peptides are attracting increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. We therefore synthesized new cyclic octapeptides conjugated with HYNIC by Fmoc solid-phase peptide synthesis. These were purified and analyzed by RP-HPLC, MALDI mass, (1)H NMR, (13)C NMR, HSQC, HMBC, COSY and IR spectroscopy. Conformational analysis of the peptides was performed by circular dichroism spectroscopy, in pure water and trifluoroethanol-water (1:1), revealed the presence of strong secondary structural features like β-sheet and random coils. Labeling was performed with (99m)Tc using Tricine and EDDA as coligands by SnCl(2) method to get products with excellent radiochemical purity99.5 %. Metabolic stability analysis did not show any evidence of breaking of the labeled compounds and formation of free (99m)Tc. Internalization studies were done and IC(50) values were determined in somatostatin receptor-expressing C6 glioma cell line and rat brain cortex membrane, and the results compared with HYNIC-TOC as standard. The IC(50) values of (99m)Tc-HYNIC-His(3)-Octreotate (21 ± 0.93 nM) and (99m)Tc-HYNIC-TOC (2.87 ± 0.41 nM) proved to be comparable. Biodistribution and image study on normal rat under gamma camera showed very high uptake in kidney and urine, indicating kidney as primary organ for metabolism and route of excretion. Biodistribution and image study on rats bearing C6 glioma tumor found high uptake in tumor (1.27 ± 0.15) and pancreas (1.71 ± 0.03). Using these findings, new derivatives can be prepared to develop (99m)Tc radiopharmaceuticals for imaging somatostatin receptor-positive tumors.

In vivo imaging of tumours using radiolabelled somatostatin (SST) analogues has become an accepted clinical tool in oncology. HYNIC-Tyr3 octreotide and Tyr3 octreotide were synthesized by FMOC solid-phase peptide synthesis using a semi-automated synthesizer. These were analyzed and purified by RP-HPLC, mass spectroscopy, IR spectroscopy, 1H NMR and 13C NMR. The prochelator 6-BOC-HYNIC was also synthesised and characterised indigenously. HYNIC-Tyr3 octreotide was labelled with 99mTc using Tricine and EDDA as coligand by SnCl2 method. Labelling with 99mTc was performed at 100 °C for 15 min and radiochemical analysis by ITLC and HPLC methods. The radiochemical purity of the complex was over 98% and log p value was found to be −1.27 ± 0.12. The stability of radiolabelled peptide complex was checked at 37 °C up to 24 h. Blood clearance and protein-binding study was also performed. In vivo biodistribution studies in rat showed uptake of 99mTc-HYNIC-TOC in kidney than any other organs. The blood clearance was faster with rapid excretion through kidneys and relatively low uptake in liver.

Palladium-catalyzed intramolecular aryl etherification reaction using bulky binaphthylphosphane ligand is shown to be a convenient method for the synthesis of seven-membered heterocy- cles. Application of this methodology to a naturally occurring pro- teinogenic L-amino acid has led to the synthesis of optically active benzoxazepine ring systems of versatile biological importance.

Radiolabeled somatostatin analogs have become powerful tools in the diagnosis and staging of neuroendocrine tumors, which express somatostatin receptors. The aim of this study was to evaluate a new somatostatin analog, 6-hydrazinopyridine-3-carboxylic acid-Ser3-octreotate (HYNIC-SATE) radiolabeled with 99mTc, using ethylenediamine-N,N'-diacetic acid and tricine as coligands, to be used as a radiopharmaceutical for the in vivo imaging of somatostatin receptor subtype 2 (SSTR2)-positive tumor. Synthesis of the peptide was carried out on a solid phase using a standard Fmoc strategy. Peptide conjugate affinities for SSTR2 were determined by receptor binding affinity on rat brain cortex and C6 cell membranes. Internalization rate of 99mTc-HYNIC-SATE was studied in SSTR2-expressing C6 cells that were used for intracranial tumor studies in rat brain. A reproducible in vivo C6 glioma model was developed in Sprague-Dawley rat and confirmed by histopathology and immunohistochemical analysis. Biodistribution and imaging properties of this new radiopeptide were also studied in C6 tumor-bearing rats. Radiolabeling was performed at high specific activities, with a radiochemical purity of96%. Peptide conjugate showed high affinity binding for SSTR2 (HYNIC-SATE IC50=1.60±0.05 n m) and specific internalization into rat C6 cells. After administration of 99mTc-HYNIC-SATE in C6 glioma-bearing rats, a receptor specific uptake of radioactivity was observed in SSTR-positive organs and in the implanted intracranial tumor and rapid excretion from nontarget tissues via kidneys. 99mTc-HYNIC-SATE is a new receptor-specific radiopeptide for targeting SSTR2-positive brain tumor and might be of great promise in the scintigraphy of SSTR2-positive tumors.

Palladium-catalyzed intramolecular aryl etherification reaction using bulky binaphthylphosphane ligand is shown to be a convenient method for the synthesis of seven-membered heterocy- cles. Application of this methodology to a naturally occurring pro- teinogenic L-amino acid has led to the synthesis of optically active benzoxazepine ring systems of versatile biological importance.