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Diabetes mellitus is a chronic metabolic disorder defined as hyperglycemia and pancreatic β-cell deterioration, leading to other complications such as cardiomyopathy. The current study assessed the therapeutic effects of phenolic acids extracted from Jasminum sambac phenols of leaves (JSP) against diabetes-induced cardiomyopathy in rats. The rats were divided into four groups, with each group consisting of 20 rats. The rats were given intraperitoneal injections of alloxan monohydrate (150 mg/kg) to induce diabetes. The diabetes-induced groups (III and IV) received treatment for six weeks that included 250 and 500 mg/kg of JSP extract, respectively. In the treated rats, the results demonstrated that JSP extract restored fasting glucose, serum glucose, and hyperlipidemia. Alloxan induced cardiomyopathy, promoted oxidative stress, and altered cardiac function biomarkers, including cardiac troponin I, proBNP, CK-MB, LDH, and IMA. The JSP extract-treated rats showed improved cardiac function indicators, apoptosis, and oxidative stress. In diabetic rats, the mRNA expression of caspase-3, BAX, and Bcl-2 was significantly higher, while Bcl-2, Nrf-2, and HO-,1 was significantly lower. In the treated groups, the expression levels of the BAX, Nrf-2, HO-1, Caspase-3, and Bcl-2 genes were dramatically returned to normal level. According to our findings, the JSP extract prevented cardiomyopathy and heart failure in the hyperglycemic rats by improving cardiac biomarkers and lowering the levels of hyperlipidemia, oxidative stress, apoptosis, hyperglycemia, and hyperlipidemia.

Ellagic acid, a natural polyphenolic compound commonly present in vegetables, fruits, nuts, and other edible plants, exerts many pharmacological activities. The present project was designed to explore the hepatoprotective effect of ellagic acid against alcohol-induced liver disease (ALD) and the correlation among alcohol, oxidative stress, inflammation, and gut microbiota. Fifty percent (v/v) alcohol (10 mL/kg bw daily) was orally administrated for 4 weeks in mice along with ellagic acid (50 and 100 mg/kg bw). Alcohol administration significantly (p < 0.05) increased the activities of alanine aminotransferase and serum aspartate aminotransferase, levels of triglyceride, low density lipoprotein, free fatty acid, and total cholesterol, and decreased contents of the high-density lipoprotein in model group compared with the control group, which were further improved by ellagic acid (50 or 100 mg/kg bw). Furthermore, daily supplementation of ellagic acid alleviated hepatic antioxidant activities (glutathione peroxidase, catalase, malondialdehyde, superoxide dismutase, and glutathione), proinflammatory cytokines levels (IL-6, IL-1β, and TNF-α), genes expressions (Tlr4, Myd88, Cd14, Cox2, Nos2, and Nfκb1), and histopathological features in alcohol-induced liver injured mice. Additionally, results also revealed that ellagic acid supplementation improved alcohol-induced gut microbiota dysbiosis. In conclusion, ellagic acid mitigated oxidative stress, inflammatory response, steatosis, and gut microbiota dysbiosis in ALD mice. Our results suggested that ellagic acid could be applied as an ideal dietary therapy against ALD.

Lysozymes are hydrolytic enzymes characterized by their ability to cleave the β-(1,4)-glycosidic bonds in peptidoglycan, a major structural component of the bacterial cell wall. This hydrolysis action compromises the integrity of the cell wall, causing the lysis of bacteria. For more than 80 years, its role of antibacterial defense in animals has been renowned, and it is also used as a preservative in foods and pharmaceuticals. In order to improve the antimicrobial efficacy of lysozyme, extensive research has been intended for its modifications. This manuscript reviews the natural antibiotic compound lysozyme with reference to its catalytic and non-catalytic mode of antibacterial action, lysozyme types, susceptibility and resistance of bacteria, modification of lysozyme molecules, and its applications in the food industry.

Nanotheranostics is an emerging frontier of personalized medicine research particularly for cancer, which is the second leading cause of death. Supramolecular aspects in theranostics are quite allured to achieve more regulation and controlled features. Supramolecular nanotheranostics architecture is focused on engineering of modular supramolecular assemblies benefitting from their mutable and stimuli-responsive properties which confer an ultimate potential for the fabrication of unified innovative nanomedicines with controlled features. Amalgamation of supramolecular approaches to nano-based features further equip the potential of designing novel approaches to overcome limitations seen by the conventional theranostic strategies, for curing even the lethal diseases and endowing personalized therapeutics with optimistic prognosis, endorsing their clinical translation. Among many potential nanocarriers for theranostics, lipid nanoparticles (LNPs) have shown various promising advances in theranostics and their formulation can be tailored for several applications. Despite the great advancement in cancer nanotheranostics, there are still many challenges that need to be highlighted to fill the literature gap. For this purpose, herein, we have presented a systematic overview on the subject and proposed LNPs as the potential material to manage cancer via non-invasive approaches by highlighting the use of supramolecular approaches to make them robust for cancer theranostics. We have concluded the review by entailing the future perspectives of lipid nanotheranostics towards clinical translation.

Introduction The most common cause of non-traumatic acute abdominal pain as well as the most common acute abdominal condition presenting to Surgical Emergency is none other than Acute Appendicitis hence it becomes the most common entity undergoing surgery in Emergencies all over the world. The lifetime risk for someone to develop acute appendicitis is 8.6% and 6.7% for males and females respectively, with 90% found in children and young adults and 10% in patients over 60 years of age.1 Increasing age or in other words decreasing immunity does affect the incidence of perforated appendix as we see the the perforation rate in acute appendicitis is approximately 20~30% but as the age goes beyond 60 years it inclines to 32-72%.2 Delay in the diagnosis caused by indefinite history and physical examination tends to contribute to higher incidence of perforated appendix as reported by Siripong et al. In another study the risk factors that were found to be associated with perforated appendicitis were male sex, fever ≥ 38°C, anorexia, and duration of pain in the pre-admission period.3 In one of the the study pre-hospital delays were exceeding related to perforation as compared to in-hospital delays which was explainable because of a linear relationship present among the pathological grade to hospital interval ratio , thus leading to increased risk of perforation.4 As far as the blood work was concerned , an increase in Total Leucocyte count with majority being polymorphonuclear leukocytes (PMN), and raised C-reactive protein (CRP) levels were found to be responsible for substantial increment in the risk and gravity of complications in appendicitis. Presence of comorbid diseases didn't show any significant affect on perforation rate.5 Objectives • To analyze the clinico-pathological profile and outcomes in patients presenting with suspected acute appendicitis. • To determine factors influencing the risk of perforation of appendix in patients presenting with acute appendicitis. • To determine the post-operative complications in patients operated on for perforated appendicitis. Our study is unique of its kind as no such study has been conducted before from this area. Although we are presenting our institution-based data, which has some limitations, but it will help in enhancing our clinical grasp of the factors, leading to perforated appendix and reduction of its incidence If possible. Material and Methods After getting approval from medical ethics board at Rawalpindi Medical University the medical records of all patients who underwent appendectomy at Surgical Unit 1 of Holy Family Hospital from 1st August 2016 to 1st August 2017 were retrospectively reviewed. Data was collected through the computerized system and manual entry register of patients at Holy Family Hospital . 100 patients who underwent emergency appendectomy in the above mentioned study period, were identified. All the patients with normal or incidental appendectomies and with incomplete medical records were excluded. The data collected included the patient's characteristics (computer record number, age, gender, education, residence, socioeconomic status), symptoms (abdominal pain, migrating pain, vomiting, fever, anorexia and diarrhea), physical examination (tenderness, rebound tenderness, guarding), laboratory investigations (Complete blood picture, Urine R/E ), and radiological findings. In addition to these variables included were co-morbids, pre hospital delay, patient delay, mode of transport, the type of operation, per operative findings, shifting of patient, and length of hospital stay, discharge status and presence of complications. Appendix was labeled as being perforated if it was mentioned so in operation notes or being confirmed by histopathology report. Patient delay was defined as the time interval, being coded in hours, from the time of onset of symptoms to the registration of patient in the emergency department. Hospital delay was defined as the time during which diagnosis was being made and patient waited for surgery. Data was entered and analyzed using Statistical Package for the Social Sciences (SPSS 16). While comparing variables, P-Value < 0.05 was considered statistically significant. A Student t test, Pearson chi-square, linear by linear association analysis was done. Result We retrospectively evaluated 100 patients with biopsy proven acute appendicitis during a tenure from August 2016 to August 2017. Sex distribution results showed male dominance with 58 males and 42 females with a mean age of 35.4 ± 2.7 years and diversity in the range (ranging from 18-95 years). Sixteen (16%) patients were in their 18-29 years of age, 33 (33%) in the age group of 30-39, 33 (33%) patients in their 40-49 years, 14 (14%) patients in their 50-59 years and only 4 (4%) patients were above 60 years old. Perforated appendicitis was found in a total of 40 patients (40%) with again male predominance, 24 (57.1%) males, and 16 (38.1%) females. Of all patients, there were 54 (54%) patients who had co-morbids; Diabetes Mellitus 27(50%), hypertension 17 (31.5%), chronic kidney diseases 6 (11.1%), and chronic obstructive airway disease 4 (7.4%). Statistically insignificant relation was seen between co-morbid conditions and risk of perforation. Pre hospital time delay was significantly longer in patients in the perforated group as compared to those in non-perforated group with p-value 38°C) at the time of presentation to the hospitals and was observed more in the perforated group of patients (51%). Tenderness and rebound tenderness in right Iliac fossa being very important clinical parameters were present in 84% and 75% patients respectively. Tenderness in right iliac fossa was 93% in the non-perforated and 73% in the perforated group while Rebound tenderness had no specific difference between the perforated and non-perforated groups. Regarding laboratory investigations, increased TLC (Total leucocyte count) > 109/L, was seen in 62 (62%) of all patients at the time of presentation. High TLC count was present in 28 (70%) patients, in the perforated group, with 92% showing left shift while 35 (58%) patients in the non-perforated group had high TLC count with 62% demonstrating a Left shift. Clinical Assessment, laboratory investigations and ultrasonography were used for diagnosis of all patients. Diagnosed mainly on clinical findings and laboratory studies were 73% patients. Ultrasound helped in the rest 27%. There was no intention to measure the sensitivity and specificity of the diagnostic tests as we only evaluated the positive cases. Postoperative complications occurred in 13 (32.5%) patients in the perforated group and in 7 (11.6%) patients in the non-perforated group (p< 0.001). Significant complications were surgical wound infection (p=0.001) and intra-abdominal sepsis and collections (p= 0.046). Two patients developed wound dehiscence both of which were in the perforated group. Patients who developed surgical site infection were managed by antimicrobial treatment and dressings with majority showing a good response. Chest infection was noted in both groups. Hospital stay in the perforation group was 7 days (3-46 days) which was longer than that of patients in the non-perforated group that is 3 days (2-23 days), and this was found to be statistically significant (p < 0.001). Of the 40 patients in the perforated appendicitis group, there were 38 (95%) patients who were discharge on complete recovery while two (5%) mortalities were reported in that group where one patient died due to sepsis, and the other one died from congestive heart failure. No mortality was reported in patients in non-perforated group. Tables: Table 1 Baseline Characteristics Non-perforated appendix (n-60) Perforated appendix (n=40) Age Group ( years) 15-25 22 (36.6%) 14 (35%) 26-50 32(53.4%) 22(55%) 51-75 6(10%) 4(10%) Gender Male 37(61.6%) 24(60%) Female 23(38.4%) 16(40%) Socioeconomic status Upper class 5(8.4%) 2(5%) Middle class 32(53.3%) 21(52.5%) Lower class 23(38.3%) 17(42.5%) Education No formal education 19(31.8%) 12(30%) Primary level 21(35%) 16(40%) Secondary level 13(21.6%) 7(17.5%) Residence Rural 37(61.6%) 26(65%) Urban 23(38.4%) 14(35%) Co-morbidities No comorbidities 34(57%) 28(30%) Diabetes 9(15%) 18(45%) Hypertension 10(16.6%) 7(17.5%) Chronic kidney disease 3(5%) 3(7.5%) COPD 4(6.4%) 0(0%) Pre-hospital delay (hours) 24 12(20%) 31(77.5%) In-hospital delay (hours) 12 15(25%) 11(27.5%) Shifted to Ward 60(100%) 38(95%) ICU 0(0%) 2(5%) Discharge status Complete recovery 60(100%) 38(95%) Mortality 0(0%) 2(5%) Postoperative complications (n=20) 7(11.6%) 13(32.5%) Table 2: Causes of delayed presentation in patients with perforated appendix Causes Frequency (%) Missed diagnosis by physician 11(28%) Managed by non-doctors 15(37%) Misperception about gravity of illness 5(12%) Financial problems 7(17%) Lack of support from the family 2(2%) Discussion Acute appendicitis being the most common cause of surgical abdomen in emergencies is managed with over all good results but when it progresses to perforation, it often leads to difficult convalescence and can even lead to death.7 In our study, perforated appendix was found in 40 patients (40%) which lies within the range reported by many other author.8,9,10,11. This high rate was also observed by some of the other authors as well and the factors contributing to it included atypical and delayed presentations, missed diagnosis, pre hospital delay, in-hospital delay and presence of co-morbids.12,13,14. Barrett et al15 studied the trends in the rate of perforation over a period of 10 years from 2001 to 2010, the distribution of these cases with respect to age showed that 55.6% of them were under 45 years of age while 15.7% patients were above 65 years while what we observed in our study was different and the percentages came out to be 66% and 4% for under 45 and above 65 years respectively showing slight less numbers in the above 65 years group however having the same trends. When risk factors were looked upon, our study showed that male gender was related significantly to perforation, which is in accordance with previous studies.16, 17. A possible explanation for this as reported by Sheu et al18, is the reluctance of males to seek healthcare services. Middle socioeconomic status and living in rural areas were considered as risk factors, in our study with possible explanation that low income, large family size and lack of approachable health care services are the reasons behind it. The same was also observed by Sirikkurnpiboon and Amornpornchareon in their study.19 Co-morbids tend to affect the clinical outcomes in surgical cases and we had a hufge number that is 54 (54%) of all patients with co-morbid conditions at presentation, yet no statistically significant association could be established between co-morbids and risk of perforation. Storm Dickerson et al also couldn't establish a significant association in their study as well.9 In several previous studies pre-hospital and in-hospital delay in appendectomies has been reported to be linked with poor outcomes.20, 21,22. In a study conducted by Busch et al23 an increased risk of perforation was seen with delay of more than 12 hours. Giraudo et al24 concluded that a delay of more than 24 hours from onset is strongly associated with risk of complications. In contrast some of the authors have shown that delaying has no association with perforation in acute appendicits. In a study conducted by Teixeira25 delay in appendectomy was not shown to be linked with an increased risk of perforation however it did show increase in the surgical site infection in the post-operative days. Likewise, Abou-Nukta et all26 also concluded that a 12 to 24 hours delay is not associated with risk of perforation. In our study, statistically significant association was established between pre-hospital delay and risk of perforation while no association could be established between in-hospital delay and perforation risk. Ideal timing for appendectomy, however, still remains debatable. Some of the factors that can be controlled include creating awareness among the people regarding early presentation to well-equipped hospitals as soon as the symptoms appear.