Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs-Comprehensive Review.

Hypertension is a highly prevalent population-level disease that represents an important risk factor for several cardiovascular complications and occupies a leading position in mortality statistics. Antihypertensive therapy includes a wide variety of drugs. Additionally, the potential antihypertensive and cardioprotective effects of several phytotherapy products have been evaluated, as these could also be a valuable therapeutic option for the prevention, improvement or treatment of hypertension and its complications. The present review includes an evaluation of the cardioprotective and antihypertensive effects of garlic, Aloe vera, green tea, Ginkgo biloba, berberine, ginseng, Nigella sativa, Apium graveolens, thyme, cinnamon and ginger, and their possible interactions with antihypertensive drugs. A literature search was undertaken via the PubMed, Google Scholar, Embase and Cochrane databases. Research articles, systematic reviews and meta-analyses published between 2010 and 2023, in the English, Hungarian, and Romanian languages were selected.

In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study.

BACKGROUND: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD). METHODS: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[18F]FDG and [68Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts. RESULTS: Due to a cellular adaptation to hypoxia, a gradual increase in [68Ga]Ga-NOTA-c(NGR) and 2-[18F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups. CONCLUSIONS: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD.

Novel Strategy in the Detection of Adverse Cutaneous Drug Reactions: A Case Series Study.

With multimorbidity on the rise, adverse cutaneous drug reactions are becoming a daily challenge in clinical practice. The objective evaluation of the skin lesion is crucial but hardly realized due to missing technology and guidelines. In this study, the novel Dermus SkinScanner-U, an optically guided high-frequency ultrasound imaging device, was evaluated regarding its comparability with the Dermatology Life Quality Index (DLQI) and the pharmacological analysis of the patients' drug therapy. A total of 40 adult patients were evaluated, all with chronic medication use and skin lesions that led to non-compliance toward the pharmacotherapy. With the ongoing aim of further improving the methodology, the first results, with two detailed patient cases, are presented here. It was concluded that in the cases evaluated, there was a significant correlation between the characteristics of the lesions observed on the optical and ultrasound image, the DLQI score, and the pharmacological analysis. The next steps include increasing the scale of the study to ultimately develop a quality-assured methodology for the correct diagnosis of skin-related adverse drug reactions and to prepare a database with the most frequently observed events.

GBSS mutations in an SBE mutated background restore the potato starch granule morphology and produce ordered granules despite differences to native molecular structure.

Potato starch with mutations in starch branching enzyme genes (SBEI, SBEII) and granule-bound starch synthase gene (GBSS) was characterized for molecular and thermal properties. Mutations in GBSS were here stacked to a previously developed SBEI and SBEII mutation line. Additionally, mutations in the GBSS gene alone were induced in the wild-type variety for comparison. The parental line with mutations in the SBE genes showed a âˆ¼ 40 % increase in amylose content compared with the wild-type. Mutations in GBSS-SBEI-SBEII produced non-waxy, low-amylose lines compared with the wild-type. An exception was a line with one remaining GBSS wild-type allele, which displayed ∼80 % higher amylose content than wild-type. Stacked mutations in GBSS in the SBEI-SBEII parental line caused alterations in amylopectin chain length distribution and building block size categories of whole starch. Correlations between size categories of building blocks and unit chains of amylopectin were observed. Starch in GBSS-SBEI-SBEII mutational lines had elevated peak temperature of gelatinization, which was positively correlated with large building blocks.

Finite Element Analysis of Various Osteotomies Used in the Treatment of Developmental Hip Dysplasia in Children.

Late-discovered developmental hip dysplasia deformities often necessitate complex surgical treatments and meticulous preoperative planning. The selection of osteotomies is contingent upon the patient's age and the specific structural deformity of the hip. In our anatomical hip model, derived from the data of a 12-year-old patient, we performed virtual osteotomies that are commonly recommended for such cases. We precisely constructed geometric models for various osteotomies, including the Dega, Pemberton, Tönnis, Ganz, Chiari pelvic, and Pauwels femoral osteotomies. We employed Autodesk Inventor for the finite element analysis of the hip joint and the corrective osteotomies. In comparing one-stage osteotomies, we noted that the Dega and Ganz pelvic osteotomies, especially when combined with the Pauwels femoral osteotomy, yielded the most favorable outcomes. These combinations led to enhanced femoral head coverage and reduced intra-articular pressure. Furthermore, we calculated the femoral head-to-acetabulum volume ratio for both the Dega and Pauwels osteotomies. The encouraging results we obtained advocate for the integration of finite element analysis in virtual osteotomies of the pelvis and femur as a preoperative tool in the management of developmental hip dysplasia.

Finite Element Analysis of Normal and Dysplastic Hip Joints in Children.

From a surgical point of view, quantification cannot always be achieved in the developmental deformity in hip joints, but finite element analysis can be a helpful tool to compare normal joint architecture with a dysplastic counterpart. CT scans from the normal right hip of an 8-year-old boy and the dysplastic left hip of a 12-year-old girl were used to construct our geometric models. In a three-dimensional model construction, distinctions were made between the cortical bone, trabecular bone, cartilage, and contact nonlinearities of the hip joint. The mathematical model incorporated the consideration of the linear elastic and isotropic properties of bony tissue in children, separately for the cortical bone, trabecular bone, and articular cartilage. Hexahedral elements were used in Autodesk Inventor software version 2022 ("Ren") for finite element analysis of the two hips in the boundary conditions of the single-leg stance. In the normal hip joint on the cartilaginous surfaces of the acetabulum, we found a kidney-shaped stress distribution in a 471,672 mm2 area. The measured contact pressure values were between 3.0 and 4.3 MPa. In the dysplastic pediatric hip joint on a patch of 205,272 mm2 contact area, the contact pressure values reached 8.5 MPa. Furthermore, the acetabulum/femur head volume ratio was 20% higher in the dysplastic hip joint. We believe that the knowledge gained from the normal and dysplastic pediatric hip joints can be used to develop surgical treatment methods and quantify and compare the efficiency of different surgical treatments used in children with hip dysplasia.

Assessment of vitamin B12 levels and cardiovascular risk factors in metformin- and non-metformin-treated type 2 diabetic patients.

Oxidative stress enhances cardiovascular risk. Metformin decreases intestinal absorption of vitamin B12. Our objective was the evaluation of type 2 diabetics focusing on differences due to their treatment. A prospective study on 224 type 2 diabetics was realized between 2015-2018 in Targu Mures, Romania, divided into 2 subgroups (metformin vs. other therapy - 2nd/3rd generation sulfonylureas, insulin, dietary regimen -, followed for at least one year) and non-diabetic controls (n=25) for oxidative stress level comparison. Serum homocysteine (HC), vitamin B12 were determined by chemiluminescence (Immulite One). Lipid peroxidation was assessed by serum malondialdehyde (MDA) measurement (HPLC). Biochemical tests, minerals, cystatin C, high-sensitivity C reactive protein (hs-CRP) were measured on Konelab20Xti, glycated hemoglobin on Nycocard Reader. GraphPad InStat-3 was used for statistics. Negative correlation occured between serum vitamin B12 and HC, this vitamin's level was significantly lower and serum zinc was significantly higher in patients on metformin. Hyperhomocysteinemia was present in 87% of the subjects, 46% had zinc deficiency and 41% elevated hs-CRP. Serum cystatin C showed positive correlation with creatinine. Serum MDA was significantly higher in diabetics compared to control patients. Elevated hs-CRP and homocysteine represent raised cardiovascular risk. Intense oxidative stress, vitamin, mineral deficiencies are frequent in diabetic subjects.

Signaling mechanism of growth hormone-releasing hormone receptor.

The hypothalamic peptide growth hormone-releasing hormone (GHRH) stimulates the secretion of growth hormone (GH) from the pituitary through binding and activation of the pituitary type of GHRH receptor (GHRH-R), which belongs to the family of G protein-coupled receptors with seven potential membrane-spanning domains. Splice variants of GHRH-Rs (SV) in human tumors and other extra pituitary tissues were identified and their cDNA was sequenced. Among the SVs, splice variant 1 (SV1) possesses the greatest similarity to the full-length GHRH-R and remains functional by eliciting cAMP signaling and mitogenic activity upon GHRH stimulation. A large body of work have evaluated potential clinical applications of agonists and antagonists of GHRH in diverse fields, including endocrinology, oncology, cardiology, diabetes, obesity, metabolic dysfunctions, Alzheimer's disease, ophthalmology, wound healing and other applications. In this chapter, we briefly review the expression and potential function of GHRH-Rs and their SVs in various tissues and also elucidate and summarize the activation, molecular mechanism and signalization pathways of these receptors. Therapeutic applications of GHRH analogs are also discussed.

Shikonin Causes an Apoptotic Effect on Human Kidney Cancer Cells through Ras/MAPK and PI3K/AKT Pathways.

(1) Background: Shikonin, the main ingredient in Chinese herbal medicine, is described as a novel angiogenesis inhibitor, and its anticancer effects have already been studied. Shikonin and its derivatives induce apoptosis and suppress metastasis, which further enhance the effectiveness of chemotherapy. However, their mechanism of function has not been completely elucidated on human renal cancer cells. (2) Methods: In our study, CAKI-2 and A-498 cells were treated with increasing concentrations (2.5-40 µM) of shikonin, when colony formation ability and cytotoxic activity were tested. The changes in the expression of the main targets of apoptotic pathways were measured by RT-qPCR and Western blot. The intracellular levels of miR-21 and miR-155 were quantified by RT-qPCR. (3) Results: Shikonin exerted a dose-dependent effect on the proliferation of the cell lines examined. In 5 µM concentration of shikonin in vitro elevated caspase-3 and -7 levels, the proteins of the Ras/MAPK and PI3K/AKT pathways were activated. However, no significant changes were detected in the miR-21 and miR-155 expressions. (4) Conclusions: Our findings indicated that shikonin causes apoptosis of renal cancer cells by activating the Ras/MAPK and PI3K/AKT pathways. These effects of shikonin on renal cancer cells may bear important potential therapeutic implications for the treatment of renal cancer.

The Management of COVID-19-Related Coagulopathy: A Focus on the Challenges of Metabolic and Vascular Diseases.

The course of COVID-19 is highly dependent on the associated cardiometabolic comorbidities of the patient, which worsen the prognosis of coronavirus infection, mainly due to systemic inflammation, endothelium dysfunction, and thrombosis. A search on the recent medical literature was performed in five languages, using the PubMed, Embase, Cochrane, and Google Scholar databases, for the review of data regarding the management of patients with a high risk for severe COVID-19, focusing on the associated coagulopathy. Special features of COVID-19 management are presented, based on the underlying conditions (obesity, diabetes mellitus, and cardiovascular diseases), emphasizing the necessity of a modern, holistic approach to thromboembolic states. The latest findings regarding the most efficient therapeutic approaches are included in the article, offering guidance for medical professionals in severe, complicated cases of SARS-CoV-2 infection. We can conclude that severe COVID-19 is closely related to vascular inflammation and intense cytokine release leading to hemostasis disorders. Overweight, hyperglycemia, cardiovascular diseases, and old age are important risk factors for severe outcomes of coronavirus infection, involving a hypercoagulable state. Early diagnosis and proper therapy in complicated SARS-CoV-2-infected cases could reduce mortality and the need for intensive care during hospitalization in patients with cardiometabolic comorbidities.

Potential Role of VHL, PTEN, and BAP1 Mutations in Renal Tumors.

The genetic profiling of renal tumors has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. The VHL, PTEN, and BAP1 genes are often mutated in renal tumors. The frequency and clinical relevance of these mutations in renal tumors are still being researched. In our study, we investigated VHL, PTEN, and BAP1 genes and the sequencing of 24 samples of patients with renal tumors, revealing that VHL was mutated at a noticeable frequency (25%). Six of the investigated samples showed mutations, and one genetic polymorphism (rs779805) was detected in both heterozygote and homozygote forms. PTEN gene mutation was observed in only one sample, and one specimen showed genetic polymorphism. In the case of the BAP1 gene, all of the samples were wild types. Interestingly, VHL mutation was detected in two female patients diagnosed with AML and in one with oncocytoma. We assume that VHL or PTEN mutations may contribute to the development of human renal cancer. However, the overall mutation rate was low in all specimens investigated, and the development and prognosis of the disease were not exclusively associated with these types of genetic alterations.

The Approach of Artificial Intelligence in Neuroendocrine Carcinomas of the Breast: A Next Step towards Precision Pathology?-A Case Report and Review of the Literature.

Primary neuroendocrine tumors (NETs) of the breast are considered a rare and undervalued subtype of breast carcinoma that occur mainly in postmenopausal women and are graded as G1 or G2 NETs or an invasive neuroendocrine carcinoma (NEC) (small cell or large cell). To establish a final diagnosis of breast carcinoma with neuroendocrine differentiation, it is essential to perform an immunohistochemical profile of the tumor, using antibodies against synaptophysin or chromogranin, as well as the MIB-1 proliferation index, one of the most controversial markers in breast pathology regarding its methodology in current clinical practice. A standardization error between institutions and pathologists regarding the evaluation of the MIB-1 proliferation index is present. Another challenge refers to the counting process of MIB-1's expressiveness, which is known as a time-consuming process. The involvement of AI (artificial intelligence) automated systems could be a solution for diagnosing early stages, as well. We present the case of a post-menopausal 79-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). The purpose of this paper is to expose the interpretation of MIB-1 expression in our patient' s case of breast neuroendocrine carcinoma, assisted by artificial intelligence (AI) software (HALO-IndicaLabs), and to analyze the associations between MIB-1 and common histopathological parameters.

Pathways of Coagulopathy and Inflammatory Response in SARS-CoV-2 Infection among Type 2 Diabetic Patients.

Chronic inflammation and endothelium dysfunction are present in diabetic patients. COVID-19 has a high mortality rate in association with diabetes, partially due to the development of thromboembolic events in the context of coronavirus infection. The purpose of this review is to present the most important underlying pathomechanisms in the development of COVID-19-related coagulopathy in diabetic patients. The methodology consisted of data collection and synthesis from the recent scientific literature by accessing different databases (Cochrane, PubMed, Embase). The main results are the comprehensive and detailed presentation of the very complex interrelations between different factors and pathways involved in the development of arteriopathy and thrombosis in COVID-19-infected diabetic patients. Several genetic and metabolic factors influence the course of COVID-19 within the background of diabetes mellitus. Extensive knowledge of the underlying pathomechanisms of SARS-CoV-2-related vasculopathy and coagulopathy in diabetic subjects contributes to a better understanding of the manifestations in this highly vulnerable group of patients; thus, they can benefit from a modern, more efficient approach regarding diagnostic and therapeutic management.

Relationship between Nutrition, Lifestyle Habits and Laboratory Parameters in Hypertensive Patients with/without Cognitive Dysfunction.

(1) Background: Cognitive dysfunction is a major concern in hypertensive patients. Lifestyle habits and nutrition influence laboratory parameters, with an impact on clinical course. The objective of the study was to evaluate nutrition and lifestyle habits in hypertensive patients with/without cognitive dysfunction and establish correlations to laboratory parameters. MATERIAL AND METHODS: 50 patients admitted to the Cardiovascular Rehabilitation Clinic in Târgu Mureș were enrolled in this study between March-June 2021. We evaluated their cognitive function, and they filled in a questionnaire about lifestyle and nutrition. Biochemical blood tests were performed using a Konelab Prime 60i analyzer. IBM-SPSS22 and GraphPad InStat3 were used for statistics. RESULTS: Mean age of hypertensive patients (n = 50) was 70.42 ± 4.82 (SD) years, half of them had cognitive dysfunction. Zinc deficiency was present in 74% of the subjects. The subgroup with cognitive dysfunction had significantly higher BMI (p = 0.009) and microalbuminuria (p = 0.0479), as well as significantly lower magnesium intake (p = 0.032) and cholesterol intake (p = 0.022), compared to those with normal cognitive status. CONCLUSIONS: Nutrition is in a close relationship with laboratory parameters; significant differences (microalbuminuria, cholesterol intake, BMI, etc.) are present between hypertensive patients with/without cognitive dysfunction. A healthy diet is important for the maintenance of metabolic balance, the achievement of optimal body weight, and the prevention of complications.

Species- and Metal-Specific Responses of the Ionome of Three Duckweed Species under Chromate and Nickel Treatments.

In this study, growth and ionomic responses of three duckweed species were analyzed, namely Lemna minor, Landoltia punctata, and Spirodela polyrhiza, were exposed for short-term periods to hexavalent chromium or nickel under laboratory conditions. It was found that different duckweed species had distinct ionomic patterns that can change considerably due to metal treatments. The results also show that, because of the stress-induced increase in leaf mass-to-area ratio, the studied species showed different order of metal uptake efficiency if plant area was used as unit of reference instead of the traditional dry weight-based approach. Furthermore, this study revealed that µXRF is applicable in mapping elemental distributions in duckweed fronds. By using this method, we found that within-frond and within-colony compartmentation of metallic ions were strongly metal- and in part species-specific. Analysis of duckweed ionomics is a valuable approach in exploring factors that affect bioaccumulation of trace pollutants by these plants. Apart from remediating industrial effluents, this aspect will gain relevance in food and feed safety when duckweed biomass is produced for nutritional purposes.

Pneumoperitoneum and Acute Kidney Injury-An Integrative Clinical Concept Review.

An increased intraabdominal pressure, particularly when occurring during periods of hemodynamic instability or fluid overload, is regarded as a major contributor to acute kidney injury (AKI) in intensive care units. During abdominal laparoscopic procedures, intraoperative insufflation pressures up to 15 mmHg are applied, to enable visualization and surgical manipulation but with the potential to compromise net renal perfusion. Despite the widely acknowledged renal arterial autoregulation, net arterial perfusion pressure is known to be narrow, and the effective renal medullary perfusion is disproportionately impacted by venous and lymphatic congestion. At present, the potential risk factors, mitigators and risk-stratification of AKI during surgical pneumoperitoneum formation received relatively limited attention among nephrologists and represent an opportunity to look beyond mere blood pressure and intake-output balances. Careful charting and reporting duration and extent of surgical pneumoperitoneum represents an opportunity for anesthesia teams to better communicate intraoperative factors affecting renal outcomes for the postoperative clinical teams. In this current article, the authors are integrating preclinical data and clinical experience to provide a better understanding to optimize renal perfusion during surgeries. Future studies should carefully consider intrabdominal insufflation pressure as a key variable when assessing outcomes and blood pressure goals in these settings.

Treatment of induced oligometastatic disease after partial response to immunochemotherapy in patient with stage IV non-small cell lung cancer and severe toxicity.

Treatment of induced oligometastatic disease after partial response to systemic antineoplastic therapy in non-small cell lung cancer (NSCLC) remains controversial. The introduction of immune checkpoint inhibitors (ICIs) has revolutionised the treatment of stage IV NSCLC. While ICI combined with chemotherapy (ChT) leads to longer duration of response and higher response rates compared with ChT alone, it can also cause serious adverse events (AEs) resulting in treatment discontinuation. In case of treatment discontinuation due to AEs after partial response to systemic treatment, surgical treatment of residual disease can be considered as it could lead to complete response. We present a case of a patient with stage IV NSCLC who is currently alive without any signs of cancer after partial response to ICI/ChT followed by surgical removal of residual disease.

Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors.

Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

High prevalence of suicide-related internet use among patients with depressive disorders - a cross-sectional study with psychiatric in-patients.

The association between Internet use and suicidal behavior is a subject of intense research. Internet use patterns of patients with depressive disorders were assessed to determine the prevalence and aim of browsing for suicide-related contents and its impact on help-seeking. Self-administered questionnaire among psychiatric in-patients treated for depression was used to assess suicidal behavior, characteristics of Internet use and help-seeking preferences. 113 psychiatric in-patients with depressive disorders participated in the study. One-third had a history of life-time suicide attempt and the majority had already encountered suicide-related contents while browsing the Internet. 27.4% reported intentional and specific search for suicidal contents. This suicide-related Internet user (SRIU) group was characterized by younger age, single status, more frequent suicidal ideations, and they more likely considered that they would attempt suicide in the future. Among patients with depressive disorders, a sub-group was identified with a potential higher suicide risk. The frequent use of the Internet and online help-seeking preference may provide an opportunity to prevent suicidal behavior in this high-risk sub-group. Further research is needed into the possibilities of using the Internet more effectively for suicide prevention.