Treatment Concepts Research Articles

Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure.

The use of an exogenous pulmonary surfactant (EPS) to deliver other relevant drugs to the lungs is a promising strategy for combined therapy. We evaluated the interaction of polymyxin B (PxB) with a clinically used EPS, the poractant alfa Curosurf (PSUR). The effect of PxB on the protein-free model system (MS) composed of four phospholipids (diC16:0PC/16:0-18:1PC/16:0-18:2PC/16:0-18:1PG) was examined in parallel to distinguish the specificity of the composition of PSUR. We used several experimental techniques (differential scanning calorimetry, small- and wide-angle X-ray scattering, small-angle neutron scattering, fluorescence spectroscopy, and electrophoretic light scattering) to characterize the binding of PxB to both EPS. Electrostatic interactions PxB-EPS are dominant. The results obtained support the concept of cationic PxB molecules lying on the surface of the PSUR bilayer, strengthening the multilamellar structure of PSUR as derived from SAXS and SANS. A protein-free MS mimics a natural EPS well but was found to be less resistant to penetration of PxB into the lipid bilayer. PxB does not affect the gel-to-fluid phase transition temperature, Tm, of PSUR, while Tm increased by ∼+ 2 °C in MS. The decrease of the thickness of the lipid bilayer (dL) of PSUR upon PxB binding is negligible. The hydrophobic tail of the PxB molecule does not penetrate the bilayer as derived from SANS data analysis and changes in lateral pressure monitored by excimer fluorescence at two depths of the hydrophobic region of the bilayer. Changes in dL of protein-free MS show a biphasic dependence on the adsorbed amount of PxB with a minimum close to the point of electroneutrality of the mixture. Our results do not discourage the concept of a combined treatment with PxB-enriched Curosurf. However, the amount of PxB must be carefully assessed (less than 5 wt % relative to the mass of the surfactant) to avoid inversion of the surface charge of the membrane.

Migraine treatment – updated recommendations 2024 –development of the Expert Group of the Headache Section ofthe Polish Neurological Society and the Polish Society for theStudy of Pain

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients qualityof life. Migraine treatment recommendations are provided based on a review of the literature from randomizedclinical trials and the consensus of a national expert panel. All available medical reference systems were screened for the range of past and present clinical studies on migraine with and without aura and on migraine-like syndromes.The results of these studies were presented in accordance with the recommendations of the Migraine Section ofthe Polish Neurological Society and the Polish Society for the Study of Pain. For the acute treatment of migraineattacks, oral non-steroidal antiinflammatory drug (NSAID), triptans and new class of drugs gepants and ditans arerecommended. The administration should follow the concept of stratified treatment. Before intake of NSAID andtriptans, oral metoclopramide is recommended. In very severe attacks, subcutaneous sumatriptan are drugs of firstchoice. Status migrainosus can be treated by cortoicosteroids, although this is not universally held to be helpful. Forthe prophylaxis of migraine, old and new drugs – betablockers flunarizine, valproic acid, and topiramate as well asmonoclonal anti CGRP antibodies, gepants and botulin toxin are drugs of first choice.

LEDT and Idebenone treatment modulate autophagy and improve regenerative capacity in the dystrophic muscle through an AMPK-pathway.

Considering the difficulties and challenges in Duchenne muscular dystrophy (DMD) treatment, such as the adverse effects of glucocorticoids, which are the main medical prescription used by dystrophic patients, new treatment concepts for dystrophic therapy are very necessary. Thus, in this study, we explore the effects of photobiomodulation (PBM; a non-invasive therapy) and Idebenone (IDE) treatment (a potent antioxidant), applied alone or in association, in dystrophic muscle cells and the quadriceps muscle, with special focus on autophagy and regenerative pathways. For the in vitro studies, the dystrophic primary muscle cells received 0.5J LEDT and 0.06μM IDE; and for the in vivo studies, the dystrophic quadriceps muscle received 3J LEDT and the mdx mice were treated with 200mg/kg IDE. LEDT and IDE treatment modulate autophagy by increasing autophagy markers (SQSTM1/p62, Beclin and Parkin) and signaling pathways (AMPK and TGF-β). Concomitantly, the treatments prevented muscle degeneration by reducing the number of IgG-positive fibers and the fibers with a central nucleus; decreasing the fibrotic area; up-regulating the myogenin and MCH-slow levels; and down-regulating the MyoD and MHC-fast levels. These results suggest that LEDT and IDE treatments enhance autophagy and prevented muscle degeneration in the dystrophic muscle of the experimental model. These findings illustrate the potential efficacy of LEDT and IDE treatment as an alternative therapy focused on muscle recovery in the dystrophic patient.

The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in comparison with the individual components (S2 and IAPinh) as well as their equimolar mixtures (S2 + IAPinh) both in vitro and in preclinical models of pancreatic and ovarian cancer. Mechanistic studies of S2/IAPinh-mediated cell death were investigated in vitro and in vivo using syngeneic and xenograft mouse models of murine pancreatic and human ovarian cancer, respectively. S2/IAPinh demonstrated markedly improved pharmacological activity in cancer cell lines and primary organoid cultures when compared to the controls. In vivo testing demonstrated a marked reduction in tumor growth rates and increased survival rates when compared to the respective control groups. The predicted mechanism of action of S2/IAPinh was confirmed through assessment of apoptosis pathways and demonstrated strong target degradation (cellular inhibitor of apoptosis proteins-1 [cIAP-1]) and activation of caspases 3 and 8. Taken together, S2/IAPinh demonstrated efficacy in models of pancreatic and ovarian cancer, two challenging malignancies in need of novel treatment concepts. Our data support an in-depth investigation into utilizing S2/IAPinh for the treatment of cancer.

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

Psychosomatic Rehabilitation for Post-COVID

Aim of the study Post-COVID is characterized by a large number of different symptoms. The indication for medical rehabilitation is based on the main symptom. Insured individuals who suffer from fatigue and have no relevant organic disorder are often rehabilitated in psychosomatic clinics. In the present study, the effectiveness of psychosomatic rehabilitation in patients with post-COVID will be investigated. Methods 91 patients with post-COVID are compared to 124 patients with mental disorders and 68 patients with cancer regarding the improvement of fatigue and depressiveness as well as satisfaction and socio-medical parameters. Results At admission, the level of fatigue did not differ in the three groups and was equally reduced. Patients with post-COVID and high depression scores at admission had clinically significant levels of fatigue at discharge. The proportion of patients with mental disorders who were discharged with a negative prognosis for employment was significantly increased. Discussion Although psychosomatic rehabilitation can reduce fatigue, the proportion of patients suffering from fatigue with post-COVID at discharge is still high. Conclusion The treatment concept for the rehabilitation of patients with post-COVID must take into account the often individual course of the disease. Psychosomatic rehabilitation can make an important contribution here.

Prevention and treatment of severe complications after radical surgery for portal cholangiocarcinoma

Aim. To develop the concept of prevention and treatment of severe complications after radical surgery for portal cholangiocarcinoma based on a comparative analysis of two periods of the surgical treatment program. Materials and methods. The study involved an analysis of multidisciplinary treatment of patients with portal cholangiocarcinoma for 8 years (2013–2020). The study consisted of two stages: program formation in 2013–2018 and evaluation of results in 2019–2020. Results. 140 patients with portal cholangiocarcinoma underwent radical or relatively radical surgery: 94 patients in the first period and 46 patients in the second period. 35 pairs of observations were formed by means of propensity score matching. In the second period, the incidence of Clavien-Dindo grade IV and V complications, CCI>40 index, duration of stay in the intensive care unit, and 90-day mortality significantly decreased. Proven reasons for the improvements included more thorough preparation of patients for the resection stage of treatment, elimination of clinical and laboratory manifestations of biliary drainage complications, careful invasive monitoring of fluid accumulations, and prevention of cholangitis. Conclusion. Maximum compensation of inflammatory and trophic disorders, elimination of jaundice, prevention and early elimination of complications as a result of their prognosis and monitoring at all stages of treatment reliably improve the immediate results of radical surgery for portal cholangiocarcinoma.

A thick wall concept for robust treatment of contacts in DEM simulation of highly polydisperse particulate systems

Modelling particulate systems with the Discrete Element Method (DEM) is an established practice, both in the representation and analysis of natural phenomena and in scale-up and optimization of industrial processes. Since the method allows tracking individual particles, each element can possess geometrical, physical, mechanical or chemical surface properties different from those of the other particles. One example is a polydisperse particulate system, i.e., characterized by a size distribution, opposed to the idealized monodisperse case. In conventional DEM, a softer particle stiffness is commonly adopted to reduce the computational time. It might happen that artificially soft particles, when colliding against a wall boundary, exhibit such large, unrealistic overlap that they “pass through” the wall and exit the domain. In the case of highly polydisperse systems, this often occurs when fine particles are pushed against the wall by coarse particles with masses several orders of magnitude larger. In the manuscript, a novel method is proposed, named thick wall, to allow the particles in contact with the walls to experience relatively large overlaps without ending up ejected out the domain. In particular, a careful way to calculate the particle-wall overlap and force unit vector can accommodate normal displacements larger than the maximum usually allowed, i.e., typically the particle radius, thereby preventing particles from being expelled from the domain. First, critical velocities for which single particles and pairs of fine/coarse particle escape the domain are analytically characterized using the linear and the Hertz models. The thick wall concept is then introduced and its effect on the maximum critical velocity is demonstrated with both contact models. Finally, application to pharmaceutical powder composed of carrier (coarse) and active pharmaceutical ingredient (API) (fine) particles in a shaken capsule prove this to be an example of vulnerability to the phenomenon of fine particle ejection and to significantly benefit from the thick wall modification.

"Window of Opportunity" in Ocular Graft-Versus-Host Disease Treatment: Results of a Longitudinal Study and Case Reports.

To perform a longitudinal study for determining the development of ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) and report cases that illustrate the "window of opportunity" concept in oGVHD treatment. Patients (n=61) were examined at prescheduled clinic visits before HSCT and three-month intervals after HSCT for 2 years. The presence or absence of oGVHD was determined using the international chronic oGVHD consensus group diagnostic criteria. Ocular surface washings (OSW) were obtained at each visit and analyzed for cytokine levels. In the longitudinal study, 26.2% (n=16; progressed group) developed either probable (11.5%, n=7) or definite oGVHD (14.8%, n=9). In the progressed group, clinically significant changes in signs (corneal staining and Schirmer I test) and symptoms at the post-HSCT visit as compared with the pre-HSCT visit occurred at 9 months. Significant differences in clinical signs and symptoms (whether average post-HSCT values or changes in values over pre-HSCT levels) between the progressed and nonprogressed groups occurred at a 9-month visit or later. In the progressed group, 55.6% of eyes that had negative matrix metalloproteinase 9 (MMP-9) test at pre-HSCT turned MMP-9 positive at 3 to 6 months post-HSCT. In the progressed group, interleukin 8 levels in OSW were significantly increased at 6 months post-HSCT. In the case reports, the "window of opportunity" was detected by MMP-9 turning positive, early corneal staining, interleukin 8 increase in OSW, and peripheral corneal epithelial thinning, which resolved with treatment initiation. A "window of opportunity" exists before patients developing symptomatic tear-deficient dry eye after HSCT for initiating treatment that may preempt oGVHD development; however, larger-scale longitudinal studies are needed for definitive recommendations.

Pedro de la Piñuela’s Bencao Bu and the Cultural Exchanges between China and the West

In the 16th and 17th centuries, Catholic missionaries in China adopted the strategy of cultural accommodation and engaged in extensive interactions with Chinese literati and the general population in order to integrate into Chinese society. They left numerous writings in the Chinese language, objectively promoting cultural exchanges between the East and the West. This article focuses on the pharmacological work Bencao Bu (本草補, Supplement to Chinese Materia Medica) by Spanish Franciscan Pedro de la Piñuela (石鐸琭, Shi Duolu, 1650–1704). The article argues that, in addition to questioning whether the works in Chinese left by missionaries have contributed to the progress of Chinese society in science, medicine, humanities and other aspects, we should also explore the process of encounter between two different cultures. Although Bencao Bu did not significantly advance Chinese medicine, la Piñuela incorporated elements of Chinese culture into the book and made an initial attempt to apply Chinese medical concepts in diagnosis and treatment. Furthermore, the book not only introduced certain Western scientific knowledge and pharmaceutical techniques but also could be considered the epitome of the global exchange of botanical knowledge and medical experiences, promoting mutual understanding between different parts of the world. This underscores the cultural significance beyond religious purposes found in Bencao Bu as well as other scientific and cultural works by missionaries during the Ming and Qing periods in China.

Professionals' Views On Forensic-Psychiatric Patients With Intellectual Disability: Impact Of Structural, Systemic And Diagnosis-Related Aspects On Treatment And Release

In forensic psychiatric clinics, patients who have committed a criminal offense on the basis of intellectual disability are also treated in according to Sect. 63 of the German Criminal Code. This group of patients has above-average lengths of stay and specific difficulties in treatment and in transition to aftercare systems are reported from practice. The present study is based on a content-analytical evaluation of ten structured interviews with practitioners of different professions who are familiar with the treatment of this patient group in forensic psychiatry. The aim was to identify treatment experiences and challenges of inpatient forensic care for this group as well as needs for change and suggestions for improvement. Respondents confirmed the specific treatment needs and person- and diagnosis-related challenges known from other studies, which were considered to be causally related to prolonged hospital stay and problems at discharge. Numerous structural and systemic barriers were also identified that impede the shortest possible forensic inpatient care and seamless transition to the non-forensic aftercare system. At the structural level, these included the need for human resources (both quantitative and qualitative) and adapted treatment concepts. Professional aftercare was considered very important for this group of patients. In this regard, the non-availability of suitable institutions, long waiting lists and reservations on the part of these institutions towards former forensic patients were identified as problems. The fact that patients with intellectual disability were less able to make their needs known than other patients and thus often received less attention from the treatment providers can be described as a systemic obstacle. This also applies to the rather high demands that the forensic system, with its goal of "improvement" through treatment, also places on people with intellectual disability. The findings of this study can contribute to improvement of the forensic inpatient care of people with intellectual disability at systemic and structural levels.

EFFects of Exposure and Cognitive behavioral Therapy for chronic BACK pain (“EFFECT-BACK”): study protocol for a randomized controlled trial

IntroductionChronic back pain is a widespread medical condition associated with high socioeconomic costs and increasing prevalence. Despite the advanced implementation of multidisciplinary approaches, providing a satisfactory treatment offer for those affected is often not possible. Exposure therapy (EXP) promises to be an effective and economical form of treatment and in a previous pilot study showed to be superior to cognitive behavioral therapy (CBT) in reducing perceived limitations of movement. The current study aims to further compare the efficacy of both treatment methods and identify those patient groups that particularly benefit from EXP.MethodsThe general objective of this randomized multicenter clinical trial (targeted N = 380) is to improve and expand the range of treatments available to patients with chronic back pain. As the primary objective of the study, two different psychological treatments (EXP and CBT) will be compared. The primary outcome measure is a clinically significant improvement in pain-related impairment, measured by the QPBDS, from baseline to 6-month follow-up. Secondary outcome measures are absolute changes and clinically significant improvements in variables coping, psychological flexibility, depressiveness, catastrophizing, exercise avoidance and fear of exercise, and intensity of pain. Participants are recruited in five psychological and medical centers in Germany and receive ten sessions of manualized therapy by trained licensed CBT therapists or clinical psychologists, who are currently in their post-gradual CBT training. Potential predictors of each treatment’s efficacy will be explored with a focus on avoidance and coping behavior.ConclusionThis study will be the first RCT to compare CBT and EXP in chronic back pain in a large sample, including patients from different care structures due to psychological and medical recruitment centers. By identifying and exploring potential predictors of symptom improvement in each treatment group, this study will contribute to enable a more individualized assignment to treatment modalities and thus improves the care situation for chronic back pain and helps to create a customized treatment program for subgroups of pain patients. If our findings confirm EXP to be an efficacious and efficient treatment concept, it should gain more attention and be further disseminated.Trial registrationClinicalTrials.gov NCT05294081. Registered on 02 March 2022.

Peritoneal Metastatic Gastric Cancer: Local Treatment Options and Recommendations.

Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.

A three-stage concept of spine pathology treatment - a different perspective.

Spinal pathologies develop in patients of all ages and may have various underlying factors. These factors include, among others, myofascial pain syndromes, disc herniation and spinal degeneration. Treatment alone, both causal and symptomatic, is not always sufficient in certain situations. The aim of this paper is to discuss the question of comprehensive treatment of spine pathologies focusing on a three-stage treatment concept. An important aspect is to determine the risk factors and their reduction, or at least modification, i.e. the first stage of the discussed treatment concept. Then, medical treatment aimed at a specific pathology, including both conservative and surgical methods, allows the cause of the pathology to be removed, i.e. the second stage of the discussed concept. And finally, timely and specialized, broadly understood rehabilitation allowing to maintain the effect of medical therapy. The implemented rehabilitation can be considered as the third stage of the discussed treatment concept.

Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria

Antimicrobial resistance is a global health threat that requires the development of new treatment concepts. These should not only overcome existing resistance but be designed to slow down the emergence of new resistance mechanisms. Targeted protein degradation, whereby a drug redirects cellular proteolytic machinery towards degrading a specific target, is an emerging concept in drug discovery. We are extending this concept by developing proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery. The anti-Mycobacterium tuberculosis (Mtb) BacPROTACs are derived from cyclomarins which, when dimerized, generate compounds that recruit and degrade ClpC1. The resulting Homo-BacPROTACs reduce levels of endogenous ClpC1 in Mycobacterium smegmatis and display minimum inhibitory concentrations in the low micro- to nanomolar range in mycobacterial strains, including multiple drug-resistant Mtb isolates. The compounds also kill Mtb residing in macrophages. Thus, Homo-BacPROTACs that degrade ClpC1 represent a different strategy for targeting Mtb and overcoming drug resistance.

Prevention and treatment of hypertensive left ventricular hypertrophy.

Left ventricular (LV) hypertrophy (LVH) is a well recognized target organ adaptation to longstanding uncontrolled hypertension and other cardiovascular risk factors. It is also a strong and independent predictor of many cardiovascular disorders. This focused review explores the current concepts in screening, diagnosis, prevention, and treatment of LVH in patients with hypertension. Currently, the primary screening and diagnostic tools for LVH are ECG and 2D echocardiography. Implementing machine learning in the diagnostic modalities can improve sensitivity in the detection of LVH. Lifestyle modifications, blood pressure control with antihypertensive therapy, and management of comorbidities aid in preventing and reversing LV remodeling. LVH is a common and often silent complication of hypertension. Prevention and reversal of LV remodeling are crucial for cardiovascular risk reduction in patients with hypertension.

The State of Systematic Therapies in Clinic for Hepatobiliary Cancers.

Hepatobiliary cancer (HBC) includes hepatocellular carcinoma and biliary tract carcinoma (cholangiocarcinoma and gallbladder carcinoma), and its morbidity and mortality are significantly correlated with disease stage. Surgery is the cornerstone of curative therapy for early stage of HBC. However, a large proportion of patients with HBC are diagnosed with advanced stage and can only receive systemic treatment. According to the results of clinical trials, the first-line and second-line treatment programs are constantly updated with the improvement of therapeutic effectiveness. In order to improve the therapeutic effect, reduce the occurrence of drug resistance, and reduce the adverse reactions of patients, the treatment of HBC has gradually developed from single-agent therapy to combination. The traditional therapeutic philosophy proposed that patients with advanced HBC are only amenable to systematic therapies. With some encouraging clinical trial results, the treatment concept has been revolutionized, and patients with advanced HBC who receive novel systemic combination therapies with multi-modality treatment (including surgery, transplant, TACE, HAIC, RT) have significantly improved survival time. This review summarizes the treatment options and the latest clinical advances of HBC in each stage and discusses future direction, in order to inform the development of more effective treatments for HBC.

Tailored surgery in the treatment of gastroesophageal cancer

The surgical options and particularly perioperative treatment, have significantly advanced in the case of gastroesophageal cancer. This progress enables a5-year survival rate of nearly 50% to be achieved through curative multimodal treatment concepts for locally advanced cancer. Therefore, in tumor boards and surgical case discussions the question increasingly arises regarding the type of treatment that provides optimal oncological and functional outcomes for individual patients with pre-existing diseases. It is therefore essential to carefully assess whether organ-preserving treatment might also be considered in the future or in what way minimally invasive or robotic surgery can offer advantages. Simultaneously, the boundaries of surgical and oncological treatment are currently being shifted in order to enable curative forms of treatment for patients with pre-existing conditions or those with oligometastatic diseases. With the integration of artificial intelligence into decision-making processes, new possibilities for information processing are increasingly becoming available to incorporate even more data into making decisions in the future.

Principle of Lok-Purush Samyata w.s.r. to Homeostasis - A Review

Man is a unique structure of the world, the structure that we see today has been continuously evolving. The structures that we see in the universe is made up of some elements, same elements could be seen in the human body structure. Everything that is in the universe is also present in the human body. Charak Samhita named this principle as Lok Purusha Samya. When there are changes in the external environment, then the environment automatically tries to return to its previous state, similarly in the human body too, when there are changes in its internal environment, then the body again returns to its previous state. An attempt is made to bring the internal environment into equilibrium, the same phenomenon is called homeostasis. The preservation of the internal environment in response to changes in the external environment is known as homeostasis. Three elements - the sun, moon, and air - maintain this cosmos in the exterior environment. The three energies of Vata, Pitta, and Kapha maintain our body in the same way as the universe. Furthermore, the fundamentals of our body are Doshas, Dhatus, and Malas. Thus, homeostasis in Ayurveda refers to the state of equilibrium between Doshas, Dhatus, and Malas, which stand for our internal environment. This article attempts to review and explain the significance of Lok-Purush Samya Siddhanta in preserving the internal environment (homeostasis). This idea also applies to the concepts of treatment, which is nothing more than the restoration of homeostasis, the body's natural state.

Indication-Specific Effect of a Phytotherapeutic Remedy on Human Fetal Osteoblastic Cells: An in vitro Analysis

Background: Impaired fracture healing is a recurring interdisciplinary medical challenge. Alternative treatment concepts, apart from conventional medicine, are popular, but scientific evidence on their effects is still lacking. Plant-derived substances are widely assumed to support bone homeostasis. To clarify the effects on bone healing mechanisms, a commercially available, homeopathic-spagyric remedy, containing inter alia two herbal substances with assumed osteogenic potential, equisetum arvense and bellis perennis, was analyzed. Methods: Human fetal osteoblastic (hFOB) 1.19 cells were incubated with the test substance in serial dilutions from 10 to 0.00001%. Cell viability has been evaluated through ATP level (CTG assay) and MTT tetrazolium reduction. Cell proliferation was analyzed by BrdU incorporation and cell migration by wound healing assay (WHA) via image analysis. Additionally, determination of the expression of key genes via real-time PCR and proteins via proteome array for inflammation, cell proliferation, and angiogenesis were performed. Results: An incubation of hFOB 1.19 cells with the test substance for 24/72 h showed no reduction in cell number, viability, or proliferation. Cell migration was unimpaired. The test substance induced inflammatory genes and growth factors along with genes of osseous regeneration (ALP, Col1, IL-1α, IL-6, IL-8, IL-10, Osteocalcin, Osteonectin, RUMX2, TGF, VEGFA). Increased protein expression was found in multiple cytokines, chemokines, and acute phase proteins. Conclusion: The test substance did not impair cell vitality parameters (MTT, CTG, BrdU, and WHA). A tendency to activate growth factors, bone regeneration genes, and proteins was shown for osteoblasts, indicating a possible positive effect on osteogenic processes.