Modulation of immune cum inflammatory pathway by earthworm granulation tissue extract in wound healing of diabetic rabbit model.

Regeneration is a rare occurrence in the animal kingdom, but the earthworm stands out as a remarkable example of this phenomenon. Recent research has highlighted the promising wound healing properties of extracts derived from earthworms. Therefore, we propose that earthworm granulation tissue extract (EGTE) may facilitate wound healing by regulating immune responses in a rabbit diabetic wound model. Electron microscopy reveals that 70 % EGTE possesses noteworthy porosity with spherical to irregularly oval configuration. Gas chromatography-mass spectrometry (GC-MS) Characterization of EGTE revealed higher levels of ergosta-5,7,22-trien-3-ol, (3. beta.,22E). In-Vitro studies revealed significant anti-oxidant, anti-inflammatory and anti-bacterial properties in dose dependent manner. Likewise, cytotoxicity assessments reveal that 70 % EGTE exhibits minimal harm to cells while displaying substantial antioxidant and anti-inflammatory activities. For In-Vivo studies excision wounds were created on the dorsal regions of the experimental animals and were divided as Group I (50 % EGTE), Group II (70 % EGTE), Group III (vehicle) and Group IV (distilled water). Over a 21-day observation period 70 % EGTE facilitated the early healing of wounds in the experimental animals, evident through prompt wound closure, granulation tissue formation, increased DNA content, enhanced tensile strength of the wound area and enhanced the expression/synthesis of wound healing markers/proteins. From these results it can be postulated that EGTE accelerates wound healing by immune modulation, dampening of inflammatory pathway and enhanced expression of growth markers. Henceforth making it promising candidate for therapeutic use in diabetic wound healing.

Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model.

Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization of α-Fe2O3-Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM, UV-visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result, FSE NCs possess huge potential for use as a possible anticancer candidate.

Syzygium cumini (L.) Extract-Derived Green Titanium Dioxide Nanoparticles Induce Caspase-Dependent Apoptosis in Hepatic Cancer Cells.

An aqueous extract of Syzygium cumini seeds was utilized to green synthesize titanium dioxide nanoparticles (TiO2 NPs). UV-Visible, DLS, FTIR, XRD, FESEM, TEM, SAED, EDAX, and photoluminescence spectroscopy techniques were employed to characterize the prepared TiO2 nanoparticles. The rutile crystal structure of TiO2 NPs was revealed by XRD study. The TEM and FESEM images of the TiO2 NPs revealed an average particle size of 50-100 nm. We employed EDAX to investigate the elemental compositions of TiO2 NPs. The O-Ti-O stretching bands appeared in the FTIR spectrum of TiO2 NPs at wavenumbers of 495 cm-1. The absorption edge peaks of TiO2 NPs were found in the UV-vis spectra at 397 nm. The MTT study revealed that TiO2 NPs effectively inhibited the growth of liver cancer Hep3 and Hep-G2 cells. The results of the corresponding fluorescent staining assays showed that TiO2 NPs significantly increased ROS generation, decreased MMP, and induced apoptosis in both liver cancer Hep3 and Hep-G2 cells. TiO2 nanoparticles lessened SOD, CAT, and GSH levels while augmenting MDA contents in Hep3 and Hep-G2 cells. In both Hep3 and Hep-G2 cells treated with TiO2 NPs, the Bax, CytC, p53, caspase-3, -8, and -9 expressions were remarkably augmented, while Bcl-2 expression was reduced. Overall, these findings revealed that formulated TiO2 NPs treatment considerably inhibited growth and triggered apoptosis in Hep3 and HepG2 cells.

Flexner has fallen: Transitions in medical education system across time, a gradual return to pre-Flexnerian state (de-Flexnerization).

The modern medical education system has gradually evolved starting from 1910 incorporating the suggestions by Abraham Flexner, his public disclosure of the poor conditions at many medical schools provided a means to galvanize all the constituencies needed for reform to occur. He could say what other reformers could not, due to their links to the medical education community. But now we are again going back to a pre-Flexnerian state due to multiple reasons such as gradually diminishing importance of basic science subjects for the students, the decline in the number and quality of investigator initiated research among clinical researchers, lesser emphasis to bedside training by means of detailed clinical examination and making appropriate observation of signs to reach to a diagnosis rather than over reliance on the laboratory tests and radiological modalities for the diagnosis, poor exposure to basic clinical skills starting from college throughout residency and the trend of disrespect and absenteeism from both theoretical and clinical/practical classes. The attitude of students is just to complete their required attendance so that they are not barred from appearing in examinations. This de-Flexnerization trend and regression to pre-Flexnerian era standards, ideologies, structures, processes, and attitudes, are bound to beget pre-Flexnerian outcomes, for you get what you designed for.

Effect of the Profit and Teaching Status of Hospitals on the Patterns and Outcomes of Abdominal Aorta and Inferior Vena Cava Injuries after Severe Abdominal Trauma.

Background: The inferior vena cava (IVC) and the abdominal aorta (AA) are two important blood vessels located in the abdomen. The outcomes of such injuries rely heavily on the experience, expertise, and resources available at the hospital where the patient is treated. However, our current understanding of the potential impact of the hospital profit and teaching status on surgical outcomes in the context of traumatic injuries to the IVC and AA remains limited, making it important to investigate the potential association between these hospital characteristics and patient outcomes to enhance the quality of care and optimize treatment strategies. Objective: This study aimed to compare demographics, trauma characteristics, and outcomes between nonprofit status (NPSH) and for-profit hospital status (FPSH), as well as among community hospitals (CHs), nonteaching hospitals (NTHs), and university hospitals (UHs), in patients with severe abdominal trauma and abdominal aorta injury (AAI), inferior vena cava injury (IVCI), and both (AAI + IVCI). Methods: Demographics, trauma, and outcome measures associated with AAI, IVCI, and AAI + IVCI were compared between the different profit and teaching status groups using NTDB. Multivariate regression was used to identify independent factors associated with death under care (DUC). Results: In the 2017 NTDB-RDS, 1,479 patients met the inclusion criteria, resulting in an overall incidence of 0.17% for AAI, IVCI, and AAI + IVCI after severe abdominal trauma. More patients died under care in the FPSH group than in the NPSH group (nonprofit vs. for-profit: 60.3% vs. 47.2%; P < 0.001). The results indicated that FPSH independently affected DUC. NTH had no significant effect on DUC; although the in-hospital complication rate varied with NTH, no independent association was observed. Conclusions: The study findings demonstrated that in patients with severe abdominal trauma, including injuries to AAI, IVCI, or both (AAI + IVCI), the profit status of hospitals, rather than the teaching status, had a substantial influence on DUC. Future studies should examine differences in the volume of cases and levels of trauma centers to better understand how to improve patient outcomes in FPSH.

Manilkara zapota L. extract topical ointment application to skin wounds in rats speeds up the healing process.

Poor circulation, unresolved inflammation, neuropathy, and infection make wound care difficult. Manilkara zapota (M. zapota) antibacterial and antioxidant properties may help speed up the healing process. The present investigation aimed to evaluate the wound healing activity of M. zapota bark ethanolic extract (MZE) by employing in-vitro migration scratch assay and in-vivo animal models. Wistar albino rats were used for the in-vivo wound healing models. No treatment was given to Group I; Group II received povidone-iodine (5% W/W); Group III received MZE (5% W/W); and Group IV received MZE (10% W/W). Linear incision models and excision wound models were used to induce injury. The ointments were applied immediately to the wounds after causing the injury. The percentage of wound contraction, the length of the epithelization period, and the wound's tensile strength were all calculated. The scratch assay assessed the test drug's potential for wound healing in-vitro. H2O2 and DPPH scavenging assays were used to measure antioxidant activity. A p < 0.05 was used to define statistical significance. On days 4, 8, 12, 16, and 20, the wound contraction potential of animals treated with MZE ointment was significantly higher (p < 0.001) than that of the control group. On day 20, the proportion of wound contraction in MZE-treated animals was 99.88%, compared to 83.86% in untreated animals. The test group had a significantly (p < 0.01) faster time to full epithelization than the control group. In the incision model, the control group had considerably lower mechanical strength (p < 0.001) than animals treated with MZE. In addition, MZE caused a significant increase (p < 0.001) in total protein and hydroxyproline levels. In the scratch experiment, test drug-treated cells showed a higher rate of cell migration than untreated cells. Furthermore, animals treated with MZE showed increased levels of epithelial tissue, collagen proliferation, and keratinization. To summarize, the current study found that M. zapota improved wound healing activity both in vitro and in vivo, as evidenced by the study results. M. zapota extract has significant wound-healing potential and could be a viable source of wound-healing nutraceuticals.

Injury characteristics and predictors of mortality in patients undergoing pancreatic excision after abdominal trauma: A National Trauma Data Bank (NTDB) study.

Pancreatic tumors and pancreatitis are the main indications for pancreatic excision (PE). However, little is known about this type of intervention in the context of traumatic injuries. Surgical care for traumatic pancreatic injuries is challenging because of the location of the organ and the lack of information on trauma mechanisms, vital signs, hospital deposition characteristics, and associated injuries. This study examined the demographics, vital signs, associated injuries, clinical outcomes, and predictors of in-hospital mortality in patients with abdominal trauma who had undergone PE. Following the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, we analyzed the National Trauma Data Bank and identified patients who underwent PE for penetrating or blunt trauma after an abdominal injury. Patients with significant injuries in other regions (abbreviated injury scale score ≥ 2) were excluded. Of the 403 patients who underwent PE, 232 had penetrating trauma (PT), and 171 had blunt trauma (BT). The concomitant splenic injury was more prevalent in the BT group; however, the frequency of splenectomy was comparable between groups. In particular, concomitant kidney, small intestine, stomach, colon, and liver injuries were more common in the PT group (all P < .05). Most injuries were observed in the pancreatic body and tail regions. The trauma mechanisms also differed between the groups, with motor vehicles accounting for most of the injuries in the BT group and gunshots accounting for most of the injuries in the PT group. In the PT group, major liver lacerations were approximately 3 times more common (P < .001). The in-hospital mortality rate was 12.4%, with no major differences between the PT and BT groups. Furthermore, there was no difference between BT and PT with respect to the location of the injuries in the pancreas, with the pancreatic tail and body accounting for almost 65% of injuries. Systolic blood pressure, Glasgow Coma Scale score, age, and major liver laceration were revealed by logistic regression as independent predictors of mortality, although trauma mechanisms and intent were not linked to mortality risk.

Traumatic injuries to the renal blood vessels and in-hospital renal complications in patients with penetrating or blunt trauma.

Background: Traumatic injuries to renal blood vessels (IRBV) can have significant consequences for patients, impacting their mortality, morbidity, and quality of life. Objective: This study aimed to compare trauma types and injury characteristics, vital signs, and outcomes in patients with and without IRBV (nIRBV) and examine whether IRBV and pre-existing renal dysfunction affected the likelihood of in-hospital renal complications (iHRC). Materials and Methods: After identifying penetrating and blunt trauma victims with IRBV in the National Trauma Data Bank, patient demographics, injury-related variables, treatment outcomes, and deaths under care were analyzed and compared. Results: Of the 994,184 trauma victims, 610 (0.6%) experienced IRBV. Victims in the IRBV group (IRBVG) had a significantly higher frequency of penetrating injuries (19.5% vs. 9.2%, P < 0.001) and higher injury severity score (ISS ≥25, 61.5% vs. 6.7%). Most injuries in both groups were unintentional, although a higher frequency of assault was noted in the IRBVG. The incidence of iHRC was higher in the IRBVG (6.6%) than in the nIRBVG (0.4%; P < 0.001). The IRBV {OR = 3.5 [95% CI = (2.4-5.0)]}, preexisting renal disorders {OR = 2.5 [95% CI = (2.1-2.9)]}, and in-hospital cardiac arrest {OR = 8.6 [95% CI = (7.7-9.5)]} were found to be among the factors associated with a higher risk of iHRC. Conclusions: IRBV and pre-existing renal disorders considerably increased the risk of developing iHRC. Due to the long- and short-term consequences of associated cardiovascular, renal, and hemodynamic complications, victims of IRBV require specialized renal management and close monitoring.

Sodium alginate encapsulated iron oxide decorated with thymoquinone nanocomposite induces apoptosis in human breast cancer cells via PI3K-Akt-mTOR pathway.

The present study investigated the cytotoxicity and proapoptotic properties of iron oxide-sodium-alginate-thymoquinone nanocomposites against breast cancer MDA-MB-231 cells in vitro and in silico. This study used chemical synthesis to formulate the nanocomposite. Electron microscopies such as scanning (SEM) and transmission (TEM), Fourier transform infrared (FT-IR), Ultraviolet-Visible, Photoluminescence spectroscopy, selected area (electron) diffraction (SAED), energy dispersive X-ray analysis (EDX), and X-ray diffraction studies (XRD) were used to characterize the synthesized ISAT-NCs and the average size of them was found to be 55 nm. To evaluate the cytotoxic, antiproliferative, and apoptotic potentials of ISAT-NCs on MDA-MB-231 cells, MTT assays, FACS-based cell cycle studies, annexin-V-PI staining, ELISA, and qRT-PCR were used. PI3K-Akt-mTOR receptors and thymoquinone were predicted using in-silico docking studies. Cell proliferation is reduced in MDA-MB-231 cells due to ISAT-NC cytotoxicity. As a result of FACS analysis, ISAT-NCs had nuclear damage, ROS production, and elevated annexin-V levels, which resulted in cell cycle arrest in the S phase. The ISAT-NCs in MDA-MB-231 cells were found to downregulate PI3K-Akt-mTOR regulatory pathways in the presence of inhibitors of PI3K-Akt-mTOR, showing that these regulatory pathways are involved in apoptotic cell death. We also predicted the molecular interaction between thymoquinone and PI3K-Akt-mTOR receptor proteins using in-silico docking studies which also support PI3K-Akt-mTOR signaling inhibition by ISAT-NCs in MDA-MB-231 cells. As a result of this study, we can conclude that ISAT-NCs inhibit the PI3K-Akt-mTOR pathway in breast cancer cell lines, causing apoptotic cell death.

Pluronic-F-127-Passivated SnO2 Nanoparticles Derived by Using Polygonum cuspidatum Root Extract: Synthesis, Characterization, and Anticancer Properties.

Nanotechnology has emerged as the most popular research topic with revolutionary applications across all scientific disciplines. Tin oxide (SnO2) has been gaining considerable attention lately owing to its intriguing features, which can be enhanced by its synthesis in the nanoscale range. The establishment of a cost-efficient and ecologically friendly procedure for its production is the result of growing concerns about human well-being. The novelty and significance of this study lie in the fact that the synthesized SnO2 nanoparticles have been tailored to have specific properties, such as size and morphology. These properties are crucial for their applications. Moreover, this study provides insights into the synthesis process of SnO2 nanoparticles, which can be useful for developing efficient and cost-effective methods for large-scale production. In the current study, green Pluronic-coated SnO2 nanoparticles (NPs) utilizing the root extracts of Polygonum cuspidatum have been formulated and characterized by several methods such as UV-visible, Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDAX), transmission electron microscope (TEM), field emission-scanning electron microscope (FE-SEM), X-ray diffraction (XRD), photoluminescence (PL), and dynamic light scattering (DLS) studies. The crystallite size of SnO2 NPs was estimated to be 45 nm, and a tetragonal rutile-type crystalline structure was observed. FESEM analysis validated the NPs' spherical structure. The cytotoxic potential of the NPs against HepG2 cells was assessed using the in vitro MTT assay. The apoptotic efficiency of the NPs was evaluated using a dual-staining approach. The NPs revealed substantial cytotoxic effects against HepG2 cells but failed to exhibit cytotoxicity in different liver cell lines. Furthermore, dual staining and flow cytometry studies revealed higher apoptosis in NP-treated HepG2 cells. Nanoparticle treatment also inhibited the cell cycle at G0/G1 stage. It increased oxidative stress and promoted apoptosis by encouraging pro-apoptotic protein expression in HepG2 cells. NP treatment effectively blocked the PI3K/Akt/mTOR axis in HepG2 cells. Thus, green Pluronic-F-127-coated SnO2 NPs exhibits enormous efficiency to be utilized as an talented anticancer agent.

Effects of Albumin-Chlorogenic Acid Nanoparticles on Apoptosis and PI3K/Akt/mTOR Pathway Inhibitory Activity in MDA-MB-435s Cells.

In this study, we synthesized, characterized, and explored the anti-microbial and anti-cancer effects of albumin-chlorogenic acid nanoparticles (NPs). Characterization studies with a UV-vis spectrophotometer, FTIR, PL spectrum, TEM, FESEM, XRD, and DLA analysis showed patterns confirming the physio-chemical nature of biogenic nanocomposites. Further, anti-microbial studies using bacterial strains Staphylococcus aureus, Streptococcus pneumonia, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Vibrio cholera, and fungal strain Candida albicans showed significant (p < 0.05) anti-bacterial and anti-fungal activities. Next, we used MDA-MB-435s, a human cell line, to evaluate the anti-cancer effects of albumin-chlorogenic acid NPs. Cytotoxic studies revealed its IC50 concentration at 24 µg/mL after a 24 h treatment of MDA-MB-435s cells. We chose this IC50 dose to analyze albumin-chlorogenic acid NPs anti-cancer effects in vitro. MDA-MB-435s cells exposed to our NPs were studied via AO/EtBr staining, cell cycle analyses via PI staining, the status of whole genomic damage via comet assay, levels of apoptotic cells via annexin V/PI staining, ROS generation via DCFH-DA staining, an assay of antioxidant enzymes catalase, superoxide dismutase, and antioxidant GSH, via ELISA analyses of apoptotic markers caspase-3, 8, 9, Bax, Bcl-2, CytC, and p53, PI3/AKT/mTOR pathway. Our results collectively showed albumin-chlorogenic acid NPs induced apoptosis via p53-dependent and PI3/AKT/mTOR inhibition in MDA-MB-435s cells. Our results denote albumin-chlorogenic acid NPs can be used as an effective candidate for anti-microbial and anti-cancer applications; however, further in vivo confirmatory studies are warranted.

Therapeutic Potential of Albumin Nanoparticles Encapsulated Visnagin in MDA-MB-468 Triple-Negative Breast Cancer Cells.

Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs' efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative.

Insight into Oncogenic Viral Pathways as Drivers of Viral Cancers: Implication for Effective Therapy.

As per a recent study conducted by the WHO, 15.4% of all cancers are caused by infectious agents of various categories, and more than 10% of them are attributed to viruses. The emergence of COVID-19 has once again diverted the scientific community's attention toward viral diseases. Some researchers have postulated that SARS-CoV-2 will add its name to the growing list of oncogenic viruses in the long run. However, owing to the complexities in carcinogenesis of viral origin, researchers across the world are struggling to identify the common thread that runs across different oncogenic viruses. Classical pathways of viral oncogenesis have identified oncogenic mediators in oncogenic viruses, but these mediators have been reported to act on diverse cellular and multiple omics pathways. In addition to viral mediators of carcinogenesis, researchers have identified various host factors responsible for viral carcinogenesis. Henceforth owing to viral and host complexities in viral carcinogenesis, a singular mechanistic pathway remains yet to be established; hence there is an urgent need to integrate concepts from system biology, cancer microenvironment, evolutionary perspective, and thermodynamics to understand the role of viruses as drivers of cancer. In the present manuscript, we provide a holistic view of the pathogenic pathways involved in viral oncogenesis with special emphasis on alteration in the tumor microenvironment, genomic alteration, biological entropy, evolutionary selection, and host determinants involved in the pathogenesis of viral tumor genesis. These concepts can provide important insight into viral cancers, which can have an important implication for developing novel, effective, and personalized therapeutic options for treating viral cancers.

Optimizing Surgical Care Amidst COVID-19: A Scoping Review of Practices and Policies.

BACKGROUND: The coronavirus disease (COVID-19) pandemic significantly disrupted surgical care worldwide, affecting different specialties in various ways. Lockdowns, surges in COVID-19 cases, and changes in hospital policies notably impacted patient attendance, management practices, and access to surgical services. This scoping review examines the adverse impacts of the COVID-19 pandemic on surgical services and the policies adopted to address these care barriers. METHODS: We conducted a comprehensive literature review using the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) guidelines. Our search, spanning 31 December 2019, to 29 January 2023, focused on understanding the multifaceted impacts of COVID-19 on surgical services, particularly across different specialties. RESULTS: An analysis of 75 articles indicated that the pandemic challenged surgeons worldwide to maintain a balance between delivering emergency and elective surgical care, and implementing safety measures against viral transmission. There was a marked decline in the surgical volume, leading to extended waitlists and decreased operating theater usage. Strategies such as prioritizing medically necessary and time-sensitive surgeries and integrating telemedicine have emerged as pivotal for ensuring the continuity of urgent care. Despite the reduced rates, essential surgeries such as appendectomies and cancer-related operations continued, yet faced hurdles, including reduced staffing, limited operating theater capacity, and complications in patient transfers. CONCLUSIONS: This review emphasizes the steep reduction in surgical service utilization at the beginning of the pandemic and emergence of new compounded barriers. Policies that designated surgeries as essential, and focused on equitable and timely access, were effective. Incorporating these findings into post-pandemic assessments and future planning is crucial to sustain adequate surgical care during similar health emergencies.

Comprehensive Highlights of the Universal Efforts towards the Development of COVID-19 Vaccine.

The world has taken proactive measures to combat the pandemic since the coronavirus disease 2019 (COVID-19) outbreak, which was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). These measures range from increasing the production of personal protective equipment (PPE) and highlighting the value of social distancing to the emergency use authorization (EUA) of therapeutic drugs or antibodies and their appropriate use; nonetheless, the disease is still spreading quickly and is ruining people's social lives, the economy, and public health. As a result, effective vaccines are critical for bringing the pandemic to an end and restoring normalcy in society. Several potential COVID-19 vaccines are now being researched, developed, tested, and reviewed. Since the end of June 2022, several vaccines have been provisionally approved, whereas others are about to be approved. In the upcoming years, a large number of new medications that are presently undergoing clinical testing are anticipated to hit the market. To illustrate the advantages and disadvantages of their technique, to emphasize the additives and delivery methods used in their creation, and to project potential future growth, this study explores these vaccines and the related research endeavors, including conventional and prospective approaches.

Topical Application of Premna integrifolia Linn on Skin Wound Injury in Rats Accelerates the Wound Healing Process: Evidence from In Vitro and In Vivo Experimental Models.

Background: When the skin and tissues within the body are injured, the healing process begins. Medicinal herbs have been used to cure wounds since time immemorial. The antimicrobial and antioxidant activity possessed by P. integrifolia may accelerate wound healing. Objectives: To assess the wound healing activity of Premna integrifolia extract (PIE) by employing in-vivo experimental animal models and an in-vitro migration scratch assay. Furthermore, to assess its cytotoxicity using the MTT assay. Methods: Wistar albino rats were used for the in vivo wound healing models. The animals were divided into four groups at random: Group I was untreated. Group II was vehicle control (ointment base). Group III was PIE ointment (5% W/W). Group IV was standard (povidone-iodine ointment) (5% W/W). The ointments were applied directly to the wounds as described above until they healed completely. The wound contraction percentage and tensile strength were calculated. The MTT test was used to determine the viability of the test extract against the fibroblast cells. The scratch assay was used in vitro to determine the wound healing potential of the test drug. P ≤ 0.05 values were considered statistically significant. Results: Premna integrifolia extract did not possess any noticeable cytotoxicity to the cell line and showed an IC50 of 185.98 µg/ml. The wound contraction potential of PIE ointment-treated animals was considerably greater (P ≤ 0.001) on days 4, 8, 12, 16, and 20 when compared to the control group. The percentage of wound contraction on day 20 was 99.92% in PIE-treated animals compared to 83.23% in untreated animals. Compared to the untreated group, the duration of full epithelization was significantly (P ≤ 0.01) shorter in the test group. When compared to the incision control group, the animals treated with PIE ointment had significantly higher (P ≤ 0.001) tensile strength. In addition, animals given the test drug had a significant (P ≤ 0.001) increase in total protein and hydroxyproline. In the in vitro scratch assay, test drug-treated cells demonstrated greater cell migration. Histology images confirmed that the test drug-treated group had epithelial tissue proliferation and keratinization. Conclusion: The current study found that Premna integrifolia improved wound healing activity both in vitro and in vivo. These findings indicate that Premna integrifolia extract has wound-healing potential and could be a viable source of nutraceuticals with wound-healing properties.

The Regularity of the Site of Impaction in Recurrent Gallstone Ileus: A Systematic Review and Meta-Analysis of Reported Cases.

Objective: Due to the rarity of recurrent gallstone ileus (RGSI), its epidemiological and clinical features are elusive. With a focus on mortality and the site of impaction, this study consolidates the key clinical characteristics of index GSI (IGSI) and RGSI. Methods: A meta-analysis of cases reported on RGSI was performed. Risk factors for mortality and site of impaction were examined, and a subgroup analysis was performed for age, sex, and site of impaction (jejunum, ileum, or others). Results: In the final analysis, 50 (56 individual cases) studies were included. The paired data for the site of impaction was available for 45 patients. Women accounted for 87.3% of all RGSI cases included in the pooled analysis. The median age (interquartile range, IQR) of the patients was 70 (63-76) years, and the median time of recurrence (IQR) was 20.5 (8.5-95.5) days. The overall mortality rate was 11.8%, without correlation between the mortality rate and age, the time of recurrence, or the site of impaction. The region in which the stone was found in RGSI and IGSI was similar in most cases (p=0.002). Logistic regression also revealed a higher probability of stone impaction in the ileum in RGSI if it was the site of impaction in IGSI. In most cases, enterolithotomy was the preferred method. Conclusions: A high index of suspicion for RGSI should be maintained for older women with a history of GSI. The region where the stone was impacted during IGSI should be investigated first in such patients.

Predictors of Superior Mesenteric Artery Syndrome: Evidence from a Case-Control Study.

Introduction Superior mesenteric artery (SMA) or Wilkie's syndrome is a rare condition arising due to compression of the third part of the duodenum between the abdominal aorta and the superior mesenteric artery. It is important to explore factors which help in suspicion and early diagnosis of the condition. The aim of this study was to find out if measurements of aortomesenteric angle and distance can predict the occurrence of SMA syndrome. Another objective was to find out if the BMI was correlated with the aortomesenteric angle and distance of the patients. Methods A retrospective hospital-based case-control study was conducted in Qimat Rai Gupta Central hospital, Haryana, India from 2018-2020. Out of total 2100 records of acute and chronic abdominal pain patients, only seven cases of Wilkie's syndrome were confirmed via Contrast-Enhanced Computed Tomography (CECT). Information on age, gender, BMI, duration of symptoms, clinical presentation, aortomesenteric angle, and distance was compared among three groups: Group I-SMA syndrome patients (N=7), Group II- acute abdominal pain patients (N=14) and Group III- chronic abdominal pain patients (N=14). Results The hospital prevalence of Wilkie's was found to be 0.3%. The median age of patients in Group I corresponded to 26 years as opposed to Group II (31.5years) and Group III (30.5 years). There was a statistically significant reduction in the aortomesenteric angle and distance of Group I patients (22º, 6mm) as compared to both Group II (52.5º, 11mm) and Group III patients (52º, 11mm). A moderate correlation of BMI was found with aortomesenteric angle (r=0.479) and distance (r=0.357). Conclusions There was a significant reduction in the aortomesenteric angle and distance of the SMA patients as compared to both patients having acute and chronic abdominal pain. The BMI of patients was positively correlated to aortomesenteric angle and distance to the moderate level. Thus BMI along with aortomesenteric angle and distance can predict the presence of SMA syndrome.