Search

Aim: Neoadjuvant chemotherapy (NAC) has transitioned from a treatment modality used solely for inoperable and locally advanced breast cancer to a therapeutic approach for early-stage breast cancer. High-risk patients, such as those with HER2-positive and triple-negative breast cancer, particularly benefit from NAC. This study aimed to evaluate the factors affecting pathological complete response (pCR) in primary breast tumors and axillary lymph nodes in patients with breast cancer. Methods: The study included female patients with breast cancer who received NAC at a training and research hospital between 2020 and 2024. Patients were categorized based on age, tumor stage, and tumor biology: luminal A, HER2-positive luminal B, HER2-negative luminal B, HER2-positive alone, or triple-negative. The presence or absence of E-cadherin in tumor cells and Ki-67 levels were also examined. Data were obtained from medical records to assess the impact of these factors on complete response in patients with breast cancer and axillary metastatic lymph nodes following NAC. Results: Univariate analysis revealed that histopathological subtypes, estrogen receptor and progesterone receptor (PR) status, HER2 status, perineural invasion, lymphovascular invasion (LVI), Ki-67 index, and carcinoma in situ (CIS) component significantly influenced pCR. Multivariate analysis confirmed that PR status [Odds ratio (OR): 3.33, 95% confidence interval (CI): 1.57-7.08, p=0.002], HER2 status (OR: 3.56, 95% CI: 1.71-7.44, p=0.001), LVI (OR: 3.91, 95% CI: 1.84-8.30, p

Objective: To evaluate the effectiveness of caudal block and penile block methods, in patients who underwent circumcision surgery in preventing postoperative pain. Materials and Methods: Patients who underwent elective circumcision surgery between January 2019 and May 2022 were retrospectively evaluated. After the exclusion criteria, 56 patients were included in the study. They were divided into two groups as penile block (group P, n=31) and caudal block (group C, n=25). Anesthesia technique applied, anesthesia duration, postoperative first micturition time, postoperative complications, time of first analgesia, analgesia need in the first six hours, observer pain score and Modified Pediatric Objective Pain Scale scores (MPOPS) were scanned. Results: When the first micturition time in the postoperative period was compared, it was found that group P took a significantly shorter time than group C (p=0.001). It was determined that group C needed analgesia in a shorter time than group P (p=0.028). When the MPOPS at 30th min (p=0.031), 90th min (p=0.043) and 6th hour (p=0.016) were compared, group C higher scores than group P. Conclusion: As a result, both methods can be used effectively and safely for appropriate pain control in patients who will undergo circumcision surgery. Both methods have advantages and disadvantages over each other. The choice of methods may vary with the experience of the surgeon and anesthetist.

This study investigates Indonesia’s ambitious artificial intelligence (AI) policy within the context of its decentralised governance structure. Through in-depth case studies in Jakarta, Central Java, and East Java, we analyse emerging AI-based policy responses and their challenges in a rapidly evolving technological landscape. Drawing from elite interviews conducted with central and local government officials and documentary research, this study offers rare insights into the local perspective on the struggle to accommodate the central government's ambitious plan with limited resources. This article finds that the divergence in the views and visions of AI between central and local governments has complicated the formulation and implementation of AI-based policies. Central authorities wield a dominant role, evident through regulatory mandates and a centralised decision-making approach that can potentially constrain local autonomy. This power asymmetry, coupled with the lack of specific AI-focused regulations, challenges local governments’ capacity to independently design and manage AI initiatives aligned with their unique contexts. Interestingly, instead of showing their resistance towards the ambitious national plan, local leaders have embraced AI policies, positioning them as innovative tools to enhance popularity in the lead-up to the 2024 general election.

Objective:To show our retrograde intrarenal surgery (RIRS) experience in anomalous kidney stones and compare its safety and efficiency with normal kidney stones.Materials and Methods:Between 2012 and 2018, patient data was reviewed retrospectively and 1700 procedures were taken into consideration. Forty-seven anomalous kidney stones were included in the study (group A). In these patients, 18 had calyx diverticulum, 12 had horseshoe kidney, 8 had ureteral duplication, 2 had ectopic kidneys, 1 had malrotation, and 1 had bifid pelvis. After making a matched pair analysis, 47 normal kidney stones with similar demographic and stone characteristics were included in our study (group N). Demographic, stone, intraoperative and postoperative data were recorded. We compared these groups regarding efficiency and safety.Results:Average scope time, hospitalization time, and postoperative double J-stent rate were higher in group A. The difference was statistically insignificant (p>0.05). Ureteral access sheath usage was higher in group N, though the difference was statistically insignificant (p=0.63). Stone-free rates and success rates were higher in group N though the difference was not statistically significant (p>0.05). The rate of complications was statistically significantly higher in group A (p=0.02).Conclusion:RIRS can be used in the management of anomalous kidney stones. It is an efficient and safe method. Prospective and larger patient numbered studies are needed.

Summary: Objective: The purpose of this study was to determine the risk factors that caused non-sentinel lymph nodes (nonSLNs) metastasis by considering the clinicopathological characteristics of patients who have 1–2 sentinel lymph node (SLN) metastasis in the clinical early stage (T1-2, N0) breast cancer. Methods: The demographic and clinicopathological characteristics of the patients were recorded retrospectively. Among these, age, size of the primary breast tumor, tumor localization and multifocality/multicentricity status, preoperative serum Neutrophil/Lymphocyte rate (NLR), c-erbB2/HER2-neu status, Estrogen Receptor (ER) and Progesterone Receptor (PR) status, primary tumor proliferation index (Ki-67), histopathological grade, molecular subtypes, histopathological subtypes, nipple/areola infiltration, Lymphatic Invasion (LI), Vascular Invasion (VI), Perineural Invasion (PNI), number of metastatic SLN m(SLN), mSLN diameter, SLN Extranodal Extension (ENE) status, and number of metastatic nonSLNs were recorded. Results: According to the univariate analysis, the HER2 positivity, Ki-67≥%20, mSLN diameter, LI, VI, PNI, ENE and molecular subtypes were found to be significant. However, the age, tumor localization, multifocality/multicentricity, T stage, ER and PR status, tumor size, histopathological grade and subtypes, nipple/areola infiltration and NLR were not found to be significant. In the multivariate analysis, significant independent predictors in nonSLN metastasis development were found to be HER2 positivity, PNI, mSLN diameter ≥10,5 mm and ENE. Conclusion: The HER2 positivity, ENE, PNI and mSLN diameter ≥10,5 mm were found to be very strong predictors in nonSLN metastasis development. The findings of this study have the potential to be a guideline for surgeons and oncologists when determining their patients' treatment plan. These components are candidates for inclusion among the clinicopathological factors that may be used in the new nomograms due to their higher sensitivity and specificity. Keywords: Axillary lymph node metastasis, Breast cancer, nonsentinel lymph node, Predictor, Sentinel lymph node

Summary: Objective: The most common complication after thyroid surgery is hypocalcaemia and it sometimes leads to problems that are difficult to correct in patients. The present study was aimed to determine the risk factors causing the development of hypocalcaemia after thyroid surgery. Methods: 818 adult patients were included in the study. The data were recorded by examining the hospital automation system and patient files retrospectively. Patients' demographic characteristics, radiological imaging findings, serum biochemical parameters, extent of the performed surgery, histopathological diagnoses were recorded. Results: The rate of hypocalcaemia was 28.4% (1.7% permanent). In multivariate analysis: the female gender (p = 0.002), heavier thyroid gland (p = 0.084), substernal location (p = 0.004) and cervical lymph nodes dissection (CLND) (p

Indonesia is a country with largest smoker in South East Asia. According to Riset Kesehatan Dasar (RISKESDAS) (2013), there is rising trends of cigarette smooking during three periods, especially in adolescents aged ≥15 years. Therefore it is necessary to take effort to prevent existence of it. Providing health promotion media in the form of hand lettering can be an alternative in providing effective information and education. Now days, Hand lettering is a popular art design for adolescents. This research was conducted on the students of class XI TKR SMK PGRI 4 Surabaya. The purpose of this study was to know the efectiveness of hand lettering as a health promotion media of harmfull effect of cigarettes in adolescents. It was quasi experimental research. Samples are 90 students of class XI TKR SMK PGRI 4 Surabaya, taken by total sampling technique. Knowledge was dependent variable, while giving treatments was independent variables. Results showed that there were differences knowledge betwween before and after hand lettering given (p = 0,000). Media effectiveness shows that hand lettering is effective for improving knowledge. It can be used as a health promotion media of harmfull effect of cigarettes in adolescents.

Isolated tuberculous epididymitis (ITE) is a rare condition affecting only the epididymis without clinical evidence of renal involvement. One of the causes of chronic scrotal pain can be ITE, which is usually only diagnosed in the presence of strong clinical suspicion, as it was in this case. The patient who had chronic scrotal pain and hydrocele and who did not respond to medical treatment for the diagnosis of epididymitis underwent scrotal exploration. The pathology material demonstrated necrotizing and non-necrotizing granulomas in the epididymis and around the small vessels. The Mantoux test performed for differential diagnosis produced a positive result. The polymerase chain reaction done on the pathology material also produced results compatible with mycobacterium tuberculosis. The patient, who did not have postoperative systemic complaints, had his scrotal pain and swelling resolved with the completion of a 6-month anti-tuberculosis medical treatment. In ITE, which is rarely encountered, patients usually present with a painless scrotal mass. It must be taken into account that ITE may unusually cause scrotal pain, and even though not emphasized thoroughly until now, it may be accompanied by hydrocele as in our patient.

Background: Favipiravir is administered orally, even against airborne RNA viruses, in a loading-dose/maintenance dose regimen. We investigated whether-(a) pulmonary delivery of favipiravir would generate high concentrations in the luminal side of the respiratory tract; and (b) avoiding first-pass metabolism by the liver by inhaled drug would generate comparable pharmacokinetics (PK) with doses significantly smaller than the oral maintenance dose., Methods: A dry powder inhalation (DPI) of favipiravir formulated by mixing with Inhalac 400® was prepared and characterized. Inhalations of ~ 120 µg dose strength, with or without a prior oral loading dose were administered to mice. Comparator mice received human-equivalent oral doses (3 mg). Three mice per sampling time point were sacrificed and favipiravir concentrations in the blood plasma, bronchio-alveolar lavage fluid (BALF) and lung tissue homogenate determined by HPLC., Results: One-compartment PK modeling of concentration-time data indicated that the area under the curve (AUC 0-24 h ) generated in the BALF recovered from mice receiving inhalations of ~ 1/25th of the oral dose subsequent to an oral loading dose was 86.72 ± 4.48 µg⋅mL -1 ⋅h. This was consistently higher than the AUC observed in the BALF of orally-dosed mice (56.71 ± 53.89 µg mL -1 ⋅h). In blood serum, the respective values of AUC were 321.55 ± 124.91 and 354.71 ± 99.60 µg⋅mL -1 ⋅h., Conclusion: Pulmonary delivery of significantly smaller doses of favipiravir generates meaningful drug disposition and pharmacokinetics at the site of respiratory viral infections. We provide the rationale for designing a self-administered, non-invasive, low-cost, targeted drug delivery system against airborne RNA virus infection., Competing Interests: Declarations. Conflict of Interest: None to declare. Generative AI declaration: No generative AI was used for any purpose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Host-directed therapy (HDT) with vitamin D in tuberculosis (TB) is beneficial only if the subject is deficient in vitamin D. We investigated pulmonary delivery of 1,25-dihydroxy vitamin D 3 (calcitriol) in mice infected with Mycobacterium tuberculosis (Mtb). We made two kinds of dry powder inhalations (DPI)- soluble particles or poly(lactide) (PLA) particles. We compared treatment outcomes when infected mice were dosed with a DPI alone or as an adjunct to standard oral anti-TB therapy (ATT). Mice infected on Day 0 were treated between Days 28-56 and followed up on Days 57, 71, and 85. Neither DPI significantly reduced Mtb colony forming units (CFU) in the lungs. Combining DPI with ATT did not significantly augment bactericidal activity in the lungs, but CFU were 2-log lower in the spleen. CFU showed a rising trend on stopping treatment, sharper in groups that did not receive calcitriol. Lung morphology and histology improved markedly in animals that received PLA DPI; with or without concomitant ATT. Groups receiving soluble DPI had high mortality. DPI elicited cathelicidin, interleukin (IL)-1 and induced autophagy on days 57, 71, and 85. Macrophage-targeted calcitriol is therefore bacteriostatic, evokes innate microbicidal mechanisms, and mitigates pathology arising from the host response to Mtb., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Genomic surveillance is crucial for tracking emergence and spread of novel variants of pathogens, such as SARS-CoV-2, to inform public health interventions and to enforce control measures. However, in some settings especially in low- and middle- income counties, where sequencing platforms are limited, only certain patients get to be selected for sequencing surveillance. Here, we show that patients with multiple comorbidities potentially harbour SARS-CoV-2 with higher mutation rates and thus deserve more attention for genomic surveillance. The relationship between the patient comorbidities, and type of amino acid mutations was assessed. Correlation analysis showed that there was a significant tendency for mutations to occur within the ORF1a region for patients with higher number of comorbidities. Frequency analysis of the amino acid substitution within ORF1a showed that nsp3 P822L of the PLpro protease was one of the highest occurring mutations. Using molecular dynamics, we simulated that the P822L mutation in PLpro represents a system with lower Root Mean Square Deviation (RMSD) fluctuations, and consistent Radius of gyration (Rg), Solvent Accessible Surface Area (SASA) values-indicate a much stabler protein than the wildtype. The outcome of this study will help determine the relationship between the clinical status of a patient and the mutations of the infecting SARS-CoV-2 virus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Azzeri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mycobacterium tuberculosis (Mtb) infection leads to upregulation of Suppressors of Cytokine signaling (SOCS) expression in host macrophages (Mϕ). SOCS proteins inhibit cytokine signaling by negatively regulating JAK/STAT. We investigated this host-pathogen dialectic at the level of transcription. We used phorbol-differentiated THP-1 Mϕ infected with Mtb to investigate preferential upregulation of some SOCS isoforms that are known to inhibit signaling by IFN-γ, IL-12, and IL-6. We examined time kinetics of likely transcription factors and signaling molecules upstream of SOCS transcription, and survival of intracellular Mtb following SOCS upregulation. Our results suggest a plausible mechanism that involves PGE2 secretion during infection to induce the PKA/CREB axis, culminating in nuclear translocation of C/EBPβ to induce expression of SOCS1. Mtb-infected Mϕ secreted IL-10, suggesting a mechanism of induction of STAT3, which may subsequently induce SOCS3. We provide evidence of temporal variation in SOCS isoform exspression and decay. Small-interfering RNA-mediated knockdown of SOCS1 and SOCS3 restored the pro-inflammatory milieu and reduced Mtb viability. In mice infected with Mtb, SOCS isoforms persisted across Days 28-85 post infection. Our results suggest that differential temporal regulation of SOCS isoforms by Mtb drives the host immune response towards a phenotype that facilitates the pathogen's survival., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to declare., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The goal of an antiviral agent research is to find an antiviral drug that reduces viral growth without harming healthy cells. Transformations of the virus, new viral strain developments, the resistance of viral pathogens, and side effects are the current challenges in terms of discovering antiviral drugs. The time has come and it is now essential to discover a natural antiviral agent that has the potential to destroy viruses without causing resistance or other unintended side effects. The pharmacological potency of thymoquinone (TQ) against different communicable and non-communicable diseases has been proven by various studies, and TQ is considered to be a safe antiviral substitute. Adjunctive immunomodulatory effects in addition to the antiviral potency of TQ makes it a major compound against viral infection through modulating the production of nitric oxide and reactive oxygen species, decreasing the cytokine storm, and inhibiting endothelial dysfunction. Nevertheless, TQ's low oral bioavailability, short half-life, poor water solubility, and conventional formulation are barriers to achieving its optimal pharmacologic benefits. Nano-formulation proposes numerous ways to overcome these obstacles through a small particle size, a big surface area, and a variety of surface modifications. Nano-based pharmaceutical innovations to combat viral infections using TQ are a promising approach to treating surmounting viral infections.

Chemotherapy of multi-drug-resistant tuberculosis (TB) requires prolonged administration of multiple drugs. We investigated whether pulmonary delivery of minute doses of drugs, along with reduced oral doses of the same agents, would affect preclinical efficacy. We prepared dry powder inhalation (DPI) formulations comprising sutezolid (SUT), the second-generation pretomanid analog TBA-354 (TBA), or a fluorinated derivative of TBA-354 (32,625) in a matrix of the biodegradable polymer poly(L-lactide). We established formulation characteristics, doses inhaled by healthy mice, and preclinical efficacy in a mouse model of TB. Oral doses of 100 mg/kg/day or DPI doses of 0.25-0.5 mg/kg/day of drugs SUT, TBA-354, or 32,625 administered over 28 days were sub-optimally effective in reducing lung and spleen burden of Mycobacterium tuberculosis (Mtb) in infected mice. The addition of 0.25-0.5 mg/kg/day of SUT, TBA-354, or 32,625 as DPI to oral doses of 50 mg/kg/day was non-inferior in clearing Mtb from the lungs of infected mice. We concluded that adjunct therapy with inhaled second-line agents has the potential to reduce the efficacious oral dose., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Diabetes mellitus is linked to both short-term and long-term health problems. Therefore, its detection at a very basic stage is of utmost importance. Research institutes and medical organizations are increasingly using cost-effective biosensors to monitor human biological processes and provide precise health diagnoses. Biosensors aid in accurate diabetes diagnosis and monitoring for efficient treatment and management. Recent attention to nanotechnology in the fast-evolving area of biosensing has facilitated the advancement of new sensors and sensing processes and improved the performance and sensitivity of current biosensors. Nanotechnology biosensors detect disease and track therapy response. Clinically efficient biosensors are user-friendly, efficient, cheap, and scalable in nanomaterial-based production processes and thus can transform diabetes outcomes. This article is more focused on biosensors and their substantial medical applications. The highlights of the article consist of the different types of biosensing units, the role of biosensors in diabetes, the evolution of glucose sensors, and printed biosensors and biosensing systems. Later on, we were engrossed in the glucose sensors based on biofluids, employing minimally invasive, invasive, and noninvasive technologies to find out the impact of nanotechnology on the biosensors to produce a novel device as a nano-biosensor. In this approach, this article documents major advances in nanotechnology-based biosensors for medical applications, as well as the hurdles they must overcome in clinical practice.

The circadian system in the human body responds to daily environmental changes to optimise behaviour according to the biological clock and also influences various physiological processes. The suprachiasmatic nuclei are located in the anterior hypothalamus of the brain, and they synchronise to the 24 h light/dark cycle. Human physiological functions are highly dependent on the regulation of the internal circadian clock. Skeletal muscles comprise the largest collection of peripheral clocks in the human body. Both central and peripheral clocks regulate the interaction between the musculoskeletal system and energy metabolism. The skeletal muscle circadian clock plays a vital role in lipid and glucose metabolism. The pathogenesis of osteoporosis is related to an alteration in the circadian rhythm. In the present review, we discuss the disturbance of the circadian rhythm and its resultant effect on the musculoskeletal system. We also discuss the nutritional strategies that are potentially effective in maintaining the system's homeostasis. Active collaborations between nutritionists and physiologists in the field of chronobiological and chrononutrition will further clarify these interactions. This review may be necessary for successful interventions in reducing morbidity and mortality resulting from musculoskeletal disturbances.

Brain metastasis is one of the major reasons of death in breast cancer (BC) patients, significantly affecting the quality of life, physical activity, and interdependence on several individuals. There is no clear evidence in scientific literature that depicts an exact mechanism relating to brain metastasis in BC patients. The tendency to develop breast cancer brain metastases (BCBMs) differs by the BC subtype, varying from almost half with triple-negative breast cancer (TNBC) (HER2 - ER - PR - ), one-third with HER2 + (human epidermal growth factor receptor 2-positive, and around one-tenth with luminal subclass (ER + (estrogen positive) or PR + (progesterone positive)) breast cancer. This review focuses on the molecular pathways as possible therapeutic targets of BCBMs and their potent drugs under different stages of clinical trial. In view of increased numbers of clinical trials and systemic studies, the scientific community is hopeful of unraveling the underlying mechanisms of BCBMs that will help in designing an effective treatment regimen with multiple molecular targets.

Background: It is unclear whether Vitamin D is efficacious as a host-directed therapy (HDT) for patients of tuberculosis (TB). We investigated pulmonary delivery of the active metabolite of Vitamin D 3 , i.e., 1, 25-dihydroxy vitamin D 3 (calcitriol) in a mouse model of infection with Mycobacterium tuberculosis (Mtb)., Methods: We optimized a spray drying process to prepare a dry powder inhalation (DPI) of calcitriol using a Quality by Design (QbD) approach. We then compared outcomes when Mtb-infected mice were treated with inhaled calcitriol at 5 ng/kg as a stand-alone intervention versus DPI as adjunct to standard oral anti-tuberculosis therapy (ATT)., Results: The DPI with or without concomitant ATT markedly improved the morphology of the lungs and mitigated histopathology in both the lungs and the spleens. The number of nodular lesions on the lung surface decreased from 43.7 ± 3.1 to 22.5 ± 3.9 with the DPI alone and to 9.8 ± 2.5 with DPI + ATT. However, no statistically significant induction of host antimicrobial peptide cathelicidin or reduction in bacterial burden was seen with the DPI alone. DPI + ATT did not significantly reduce the bacterial burden in the lungs compared to ATT alone., Conclusions: We concluded that HDT using the low dose calcitriol DPI contributed markedly to mitigation of pathology, but higher dose may be required to evoke significant induction of bactericidal host response and bactericidal activity in the lung., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Transient transfection of the respiratory mucosa of mice infected with Mycobacterium tuberculosis (Mtb) with gamma interferon (IFN-γ) promises benefits in disease therapy. We investigated preclinical efficacy of a dry powder inhalation (DPI) as a stand-alone versus adjunct to oral anti-tuberculosis (TB) chemotherapy in mice. We observed that this host-directed therapy mitigates the gross organ pathology and histopathology of lung and spleen tissue of infected mice receiving the DPI, either alone or as adjunct therapy. However, no statistically significant reduction in Mtb colony forming units (CFU) occurred if mice were given only DPI; but not drugs. We compared one and three doses a week of the DPI over four weeks; with or without concomitant oral drugs. There was no significant difference in lung CFU after four or 12 doses of the DPI alone, but, surprisingly, four doses were qualitatively better than 12 doses in mitigating lung pathology. Nodular lesions on the lung surface and the area occupied by these was significantly reduced after four doses of the DPI, even without oral drugs. Transient transfection with IFN-γ did not induce pathological inflammation of the lungs and airways. We conclude that IFN-γ, as expected of host-directed therapy, 'heals the host; ' but does not 'kill the bug.', (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (Copyright © 2022 Yasaman Taheri et al.)

The development and spread of resistance to antimicrobial drugs is hampering the management of microbial infectious and wound healing processes. Curcumin is the most active and effective constituent of Curcuma longa L., also known as turmeric, and has a very long and strong history of medicinal value for human health and skincare. Curcumin has been proposed as strong antimicrobial potentialities and many attempts have been made to determine its ability to conjointly control bacterial growth and promote wound healing. However, low aqueous solubility, poor tissue absorption and short plasma half-life due its rapid metabolism needs to be solved for made curcumin formulations as suitable treatment for wound healing. New curcumin nanoformulations have been designed to solve the low bioavailability problem of curcumin. Thus, in the present review, the therapeutic applications of curcumin nanoformulations for antimicrobial and wound healing purposes is described., (© 2021 John Wiley & Sons, Ltd.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has changed the global scenario. To date, there are no treatment or preventive options. The discovery of a new drug will take time. In addition, the new drug will have side effects, and the virus will gradually become resistant to it. Therefore, it is important to search for a drug with a natural origin., Objective: In this review, we analyzed and summarized various ethnomedicinal plants and their bioactive compounds as a source of antiviral agents for COVID-19 prevention and treatment., Methods: From the literature, we selected different natural compounds that can act as potential targets at low cost with broad-spectrum antiviral activity., Results: Of the 200 Chinese herbal extracts tested for their possible role against SARS-CoV, Lycoris radiata, Artemisia annua, Pyrrosia lingua, and Lindera aggregate showed anti-SARS-CoV effects with the median effective concentration = 2.4-88.2 μg/mL., Conclusion: Ethnomedicinal herbs can be used as an alternative source of novel, promising antiviral agents that might directly or indirectly inhibit the COVID-19 progression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The bifunctional alcohol/aldehyde dehydrogenase (AdhE) comprises both an N-terminal aldehyde dehydrogenase (AldDH) and a C-terminal alcohol dehydrogenase (ADH). In vivo, full-length AdhE oligomerizes into long oligomers known as spirosomes. However, structural analysis of AdhE is challenging owing to the heterogeneity of the spirosomes. Therefore, the domains of AdhE are best characterized separately. Here, the structure of ADH from the pathogenic Escherichia coli O157:H7 was determined to 1.65 Å resolution. The dimeric crystal structure was confirmed in solution by small-angle X-ray scattering., (open access.)

Alcoholic liver disease (ALD) is a broad-spectrum disorder, covering fatty liver, cirrhosis, alcoholic hepatitis and in extreme untreated condition hepatocellular carcinoma (HCC) may also develop. Cladonia rangiferina (CR) is a class of lichen having a broad spectrum of pharmacological activity. It is used like traditional natural sources in ancient times in India, China, Sri Lanka, etc. Folkloric record about CR has reported their use as an antimicrobial, antitumor, antioxidant, anti-inflammatory activities, etc. Hence, the present study was requested to ascertain the effect of the ethanolic extract of Cladonia rangiferina (CRE) on alcohol-induced hepatotoxicity. The animals were evaluated for the estimation of the liver in vivo biochemical antioxidant parameters. The liver tissues were further evaluated histopathologically and western blotting examination for localization of apoptotic gene expression that plays a pivotal role in hepatotoxicity. The results of this study reveal that CRE proves to be helpful in the treatment of alcohol-induced hepatotoxicity and oxidative stress. Results of different markers have shown that among all, CRE has demonstrated the best hepatoprotective activity. These observations say about the importance of the components of the extract. The ameliorative action of CRE in alcoholic liver damage may exist due to antioxidant, anti-inflammatory, and anti-apoptotic activities., (© 2020 The Author(s).)

Convolvulus genus is a representative of the family of Convolvulaceae. Convolvulus plants are broadly distributed all over the world and has been used for many centuries as herbal medicine. Convolvulus genus contains various phytochemicals such as flavonoids, alkaloids, carbohydrates, phenolic compounds, mucilage, unsaturated sterols or terpenes, resin, tannins, lactones, and proteins. This review highlights the phytochemical composition, antimicrobial and antioxidant activities, application as food preservative, traditional medicine use, anticancer activities, and clinical effectiveness in human of Convolvulus plants. All the parts of Convolvulus plants possess therapeutic benefits; preliminary pharmacological data validated their use in traditional medicine. However, further preclinical and clinical experiments are warranted before any application in human health., (© 2019 John Wiley & Sons, Ltd.)

Traditional Pertinence: Argyreia speciosa Sweet (Linn.), belongs to the family convolvulaceae, a traditional Indian medicinal herb, has been used to treat acute/chronic ulcers, gonorrhea, rheumatoid arthritis and several nervous disorders having a long history., Aim of the Study: A broad spectrum approach of this work was to find out the antioxidant activity of Argyreia speciosa seeds, in vitro and in vivo antioxidant assay were performed., Material and Methods: Total phenolic content (TPC), reducing power (RP), antioxidant activity (AOA), O 2 · - (superoxide anion), DPPḢ (1,1-diphenyl-2-picrylhydrazyl) and ˙OH (hydroxyl) radicals scavenging activities, GSH (glutathione), CAT (catalase), SOD (superoxide dismutase) and LPO (lipid peroxidase) are the major parameters which were studied for determining in vitro and in vivo antioxidant property of seed extract & their six fractions obtained from A. speciosa . Carbon tetrachloride (CCl 4 ) induced rat model was used to determine in vivo antioxidant assay of extract and its fractions., Results: Butanol fraction (AS-BF) showed strong antioxidant property and protected oxidative DNA damage. AS-BF was found best as compared to all other fraction for determining antioxidant property of seeds with the reduction in lipid peroxide formation and increment in GSH, CAT and SOD. AS-BF showed the presence of phenolic compounds viz. gallic acid, chlorogenic acid, and ellagic acid., Conclusion: From these results, it was proved that A. speciosa seeds prevent tissue damage due to oxidative stress with strong antioxidant activity., Competing Interests: None., (© 2019 The Author(s).)

Aldehyde-alcohol dehydrogenase (AdhE) is a key enzyme in bacterial fermentation, converting acetyl-CoA to ethanol, via two consecutive catalytic reactions. Here, we present a 3.5 Å resolution cryo-EM structure of full-length AdhE revealing a high-order spirosome architecture. The structure shows that the aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) active sites reside at the outer surface and the inner surface of the spirosome respectively, thus topologically separating these two activities. Furthermore, mutations disrupting the helical structure abrogate enzymatic activity, implying that formation of the spirosome structure is critical for AdhE activity. In addition, we show that this spirosome structure undergoes conformational change in the presence of cofactors. This work presents the atomic resolution structure of AdhE and suggests that the high-order helical structure regulates its enzymatic activity.

Background: Reindeer lichen, Lichen rangiferinus syn. or Cladonia rangiferina (L.) F. H. Wigg. (Cladoniaceae) has been traditionally reported as a remedy to treat fever, colds, arthritis as well as convulsions, liver infections, coughs, constipation, and tuberculosis. The current study is aimed at rectification of alcohol induced liver damage by the use of L. rangiferinus extract., Objectives: The aim of the study was to compare some biochemical markers for liver injury and hematological indices in normal untreated rats and treated rats., Material and Methods: The study was performed using male Wistar rats. Animals were categorized into five groups, negative control group (normal diet only), treated groups (2 groups were lichen treated along with 10% ethanol & 1 group was only ethanol treated) and positive control group (Silymarin+10% ethanol) of six animals in each group. Biochemical markers for liver injury and hematological indices of all animals were measured using standard diagnostic tools. The animals were then sacrificed and livers were sent to the pathology lab for histopathological analysis., Results: Lichen extract showed a significant restoration of altered biochemical parameters towards normal in both in vitro and in vivo conditions. The total phenolic and flavonoid content of the LRE was found to be 21.78 μg PE/mg of extract and 5.13 μg RE/mg of extract respectively. The IC 50 values for atranorin and fumarprotocetraric acid were found to be 128.48 and 218.46 mg/mL respectively. Reducing power of the extract was found to be quite significant. After administration of lichen extract, endothelial cells were less injured around central vein and number of fat vacuoles was also lesser in hepatocytes., Conclusion: Conclusively, treatment with lichen extract assuages alcohol-related damage and guards hepatic tissue from alcohol-induced toxicity., (Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

Wound healing is a complex process in which injured skin and tissues repaired by interaction of a complex cascade of cellular events that generates resurfacing, reconstitution and restoration of the tensile strength of injured skin. It follows β-catenin, extracellular signal regulated kinase (ERK) and Akt signaling pathways. Aegle marmelos L., generally known as bael is found to act as anti-inflammatory, antioxidant and anti-ulcer agent. Furthermore, studies have demonstrated that this Indian traditional medicinal plant, A. marmelos flower extract (AMF) was used for wound injury. Henceforth, the current study was investigated to ascertain the effect of its active constituents in vitro wound healing with mechanism involve in migration of cells and activation of β-catenin in keratinocytes, inhibition of PGE 2 in macrophages and production of collagen in fibroblasts. We have taken full thickness wound of rats and applied AMF for 2 weeks. Cutaneous wound healing activity was performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW264.7 macrophages to determine cell viability, nitric oxide production, collagen expression, cell migration and β-catenin activation. Results shows that AMF treated rats demonstrated reduced wound size and epithelisation was improved, involved in keratinocytes migration by regulation of Akt signaling, beta-catenin and extracellular signal-regulated kinase (ERK) pathways. AMF and its active constituent's increased mRNA expression, inhibited nitric oxide, PGE 2 release, mRNA expression of mediators in RAW 264.7 macrophages and enhances the motility of HaCaT keratinocytes in vitro wound healing of rats.

To initiate infection, many viruses enter their host cells by triggering endocytosis following receptor engagement. However, the mechanisms by which non-enveloped viruses escape the endosome are poorly understood. Here we present near-atomic-resolution cryo-electron microscopy structures for feline calicivirus both undecorated and labelled with a soluble fragment of its cellular receptor, feline junctional adhesion molecule A. We show that VP2, a minor capsid protein encoded by all caliciviruses 1,2 , forms a large portal-like assembly at a unique three-fold axis of symmetry, following receptor engagement. This assembly-which was not detected in undecorated virions-is formed of twelve copies of VP2, arranged with their hydrophobic N termini pointing away from the virion surface. Local rearrangement at the portal site leads to the opening of a pore in the capsid shell. We hypothesize that the portal-like assembly functions as a channel for the delivery of the calicivirus genome, through the endosomal membrane, into the cytoplasm of a host cell, thereby initiating infection. VP2 was previously known to be critical for the production of infectious virus 3 ; our findings provide insights into its structure and function that advance our understanding of the Caliciviridae.

Aims: Ritonavir (RIT) is a human immune deficiency virus (HIV) protease inhibitor (PI) active against HIV-1 and HIV-2. Among various adverse effects of PIs, hepatotoxicity is a very common adverse reaction of RIT which is concentration dependent. Red clover isoflavones are found to possess anti-inflammatory, antioxidant and anti-apoptosis activity. Furthermore, recent studies have demonstrated that these isoflavones can be used to alleviate the side-effects of drugs. Hence, the present study was inquested to ascertain the effect of Formononetin (FMN) and Biochanin A (BCA) on RIT induced hepatotoxicity., Main Methods: Five groups of animals were subjected to treatment as control, toxic control (RIT), third group (RIT + FMN), fourth group (RIT + BCA), the fifth group (RIT + FMN + BCA) and sixth group (FMN + BCA) for 14 days. The animals were evaluated for estimation of liver toxicity markers, inflammatory biomarkers, in-vivo biochemical antioxidant parameters. The liver tissues were further evaluated histopathologically and western blotting examination for localization of apoptotic gene expression that plays a pivotal role in hepatotoxicity., Key Findings: FMN and BCA ameliorated the increased levels of biochemical markers of liver, attenuated the RIT induced Bax, caspase-3, NFκB and eNOS activation and persuaded the Bcl 2 and pAkt level. Alteration in the levels of inflammatory markers was also observed in both hepatic tissue and serum., Significance: FMN and BCA exerts hepatoprotective effect through modulating the oxidative stress, inflammation, apoptosis and reversing the tissue degeneration suggesting its therapeutic role in hepatotoxicity and other hepatocellular diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Euphorbia hirta possesses antibacterial, anti-inflammatory, galactogenic, antidiarrheal, antioxidant, hypoglycemic, antiasthmatic, antiamebic, antifungal, and antimalarial activities., Objective: The overall objective of the current study was the investigation of the whole plant extract of E. hirta and flavonoids from E. hirta on gastroesophageal reflux disease (GERD) in rats., Materials and Methods: The whole plant extract of E. hirta was characterized by analysis of flavonoids (HPLC: HPLC, UV, IR, MS and 1 HNMR). GERD model was induced surgically in Wistar rats under pentobarbitone sodium anesthesia (50 mg/kg, i.p.) and the tissue esophagus and stomach were removed. The tissues were washed with physiological saline and were examined for GERD. The whole plant extract of E. hirta in doses of 50, 100, and 200 mg/kg were administered orally twice daily at 10:00 and 16:00 hours, respectively, for 5 days and kaempferol (100 mg/kg) or omeprazole (OMZ) in the dose of 30 mg/kg 1 hour prior to the induction of GERD. Control groups received suspension of 1% carboxymethyl cellulose in distilled water (10 mL/kg)., Results: The levels of gastric wall mucus increased and of plasma histamine and H + , K + ATPase significantly decreased in groups treated by both the plant extract and flavonoids. Both the plant extract and flavonoids reduced the lipid peroxidation and superoxide dismutase and increased the levels of catalase and reduced glutathione., Conclusions: The whole plant extract of E. hirta is attributed to its antisecretory, gastroprotective, and antioxidant potential as that of quercetin, rutin, kaempferol, and proton pump blocker (omeprazole) to treat GERD., Summary: The aqueous extract of whole plant of Euphorbia hirta revealed the presence of kaempferol (0.0256%), quercetin (0.0557%), and rutin (0.0151%), and the ethyl acetate fraction of whole plant of E. hirta possesses kaempferol (0.0487%), quercetin (0.0789%), and rutin (0.0184%).The levels of gastric wall mucus increased and of plasma histamine and H + -K + -ATPase significantly decreased in rats groups treated by both the whole plant extract of E. hirta and flavonoids.Both the whole plant extract of E. hirta and flavonoids reduced the lipid peroxidation and superoxide dismutase and increased the levels of catalase and reduced glutathione in rats groups. Abbreviation used: 1HNMR: Proton Nuclear Magnetic Resonance Spectroscopy, CAT: Catalase, EHAE: Aqueous extract of Euphorbia hirta, EHEF: Ethyl Acetate Fractions of Euphorbia hirta, GERD: Gastroesophageal reflux disease, GSH: Reduced Glutathione, HPLC: High performance liquid chromatography, IR: Infrared spectroscopy, LPO: Lipid Peroxidase, MDA: Malondialdehyde, MS: Mass Spectroscopy, OMZ: Omeprazole, ROS: Reactive Oxygen Species, SOD: Superoxide dismutase, TBHQ: tert-Butylhydroquinone, TLC: Thin Layer Chromatography, UV: Ultraviolet, UV: Ultraviolet-Visible Spectroscopy., Competing Interests: There are no conflicts of interest.