Bone Marrow Adipocytes—Role in Physiology and Various Nutritional Conditions in Human and Animal Models

In recent years, adipose tissue has attracted a lot of attention. It is not only an energy reservoir but also plays important immune, paracrine and endocrine roles. BMAT (bone marrow adipose tissue) is a heterogeneous tissue, found mostly in the medullary canal of the long bones (tibia, femur and humerus), in the vertebrae and iliac crest. Adipogenesis in bone marrow cavities is a consequence of ageing or may accompany pathologies like diabetes mellitus type 1 (T1DM), T2DM, anorexia nervosa, oestrogen and growth hormone deficiencies or impaired haematopoiesis and osteoporosis. This paper focuses on studies concerning BMAT and its physiology in dietary interventions, like obesity in humans and high fat diet in rodent studies; and opposite: anorexia nervosa and calorie restriction in animal models.     

Implications of SCFAs on the Parameters of the Lipid and Hepatic Profile in Pregnant Women

Short-chain fatty acids (SCFAs) are the product of the anaerobic intestinal bacterial fermentation of dietary fiber and resistant starch. An abnormal intestinal microbiota may cause a reduction in the production of SCFAs, which stimulate the development of intestinal epithelial cells, nourish enterocytes, influence their maturation and proper differentiation, reduce the pH, and are an additional source of energy for the host. There have been reports of the special role of SCFAs in the regulation of glucose and lipid metabolism during pregnancy. Aim: The aim of the study was to analyze the correlation of SCFAs with lipid and hepatic metabolism during pregnancy in relation to the body weight of pregnant women. Material and methods: This study was conducted in pregnant women divided into two groups: Obese (OW—overweight and obese women; n = 48) and lean (CG—control group; n = 48) individuals. The biochemical plasma parameters of lipid metabolism (TG, CH, LDL, HDL), inflammation (CRP), and liver function (ALT, AST, GGT) were determined in all of the subjects. SCFA analysis was performed in the stool samples to measure acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0 i), butyric acid (C 4:0 n), isovaleric acid (C 5:0 i) valeric acid (C 5:0 n), isocaproic acid (C 6:0 i), caproic acid (C 6:0 n), and heptanoic acid (C 7:0). Results: Statistically significant differences in the concentrations of C 3:0 and C 6:0 n were found between women in the OW group compared to the CG group. The other SCFAs tested did not differ significantly depending on BMI. The C 2:0, C 3:0, and C 4:0 n ratios showed differences in both OW and CG groups. In the OW group, no relationship was observed between the concentrations of the SCFAs tested and CRP, ALT, AST. A surprising positive relationship between C 5:0 n and all fractions of the tested lipids and branched C 5:0 with CHL, HDL, and LDL was demonstrated. In the OW group, HDL showed a positive correlation with C 3:0. However, lower GGT concentrations were accompanied by higher C 4:0 and C 5:0 values, and this tendency was statistically significant. Conclusions: The results of our research show that some SCFAs are associated with hepatic lipid metabolism and CRP concentrations, which may vary with gestational weight. Obesity in pregnancy reduces the amount of SCFAs in the stool, and a decrease in the level of butyrate reduces liver function.     

Open reduction,Dega osteotomy and proximal femoral osteotomy in delayed diagnosis of developmental hip dislocation: outcome at 40-year follow-up

PurposeLate-diagnosed dislocated hips underwent open reduction, Dega osteotomy, and proximal femoral osteotomy between 1968 and 1988. The objectives of this study are to assess the survival of hips into adulthood, clinical and radiological outcome, patients’ life perspectives and the risk factors of failure.MethodsAn assessment of 67 hips treated when younger than five years (<age 5yr. group) and 71 hips in the group aged older than five years (+age 5yr.) was performed. All cases were evaluated clinically and radiographically, and survival was assessed, considering hip replacement as endpoints for failure (abbreviation HR+ refers to hips that underwent hip replacement surgery; HR- refers to hips that have not been replaced at the follow-up). The fertility rate and the social security disability benefits (SSDB) recipiency percentage were calculated.ResultsThe 40-year survival rates were 73% (95% confidence (CI) 71% to 76%) in the <age 5yr. group, 54% (95% CI 51% to 57%) in the +age 5yr. group, 70% (95% CI 67% to 73%) in one-sided dislocations and 57% (95% CI 54% to 60%) in bilateral dislocations. At follow-up, the median Harris hip and Western Ontario and McMaster Universities Osteoarthritis scores were 90.0 and 13.0 (<age 5yr. group, HR-), 74.0 and 28.0 (+age 5yr. group, HR-), 90.0 and 16.0 (<age 5yr. group, HR+) and 84.5 and 11.5 (+age 5yr. group, HR+), respectively. The operation normalized the radiological parameters. The correlation between the grade of femoral head avascular necrosis (AVN) at a median 2.6 years after the operation and the grade of osteoarthritis at follow-up was 0.38 (p < 0.001). The fertility rate was 1.54. In total, 16.0% (aged under five years) and 38.5% (aged over five years) of patients were receiving SSDB (p = 0.003).ConclusionEarly failure risk factors are older age at the surgical procedure, high AVN grade and bilateral hip involvement. Still, the results facilitate hip reposition whenever technically manageable, even in teenagers.Level of evidenceIII     

Rapid rise in plasma glucagon induced by acute cold exposure in man and rat

The effect of acute cold exposure on the concentration of glucagon in the blood was investigated in man and in intact and adrenalectomized rats.In man fasted overnight acute cold exposure, which caused a twofold increase in O₂-consumption resulted in a rapid rise in plasma glucagon. The levels of insulin and blood glucose remained unaltered, while the concentration of serum free fatty acids and -hydroxybutyrate increased.In fasted intact rats acute cold exposure lead to similar effects. A close parallelism between the rise in plasma glucagon and the concentration of hepatic cycloAMP was observed. Adrenalectomy did not impair the cold induced rise in plasma glucagon and hepatic cycloAMP.It is concluded that acute cold exposure caused a rapid rise in the concentration of plasma glucagon leading to an increase in the concentration of hepatic cycloAMP, thus enhancing the rate of hepatic gluconeogenesis and ketogenesis. As these alterations were similar in the absence of glucocorticoids and medulla-derived catecholamines, it is suggested that glucagon may play a role in the metabolic adaptation to acute cold exposure.     

Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.

PURPOSE: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells. EXPERIMENTAL DESIGN: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors. RESULTS: PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals. CONCLUSIONS: COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination.     

Dietary factors and cancers of breast, endometrium, and ovary: Strategies for modifying fat intake in African American women

Modification of dietary fat and fiber could help prevent cancers of the breast, endometrium, and ovary that are prevalent in African-American women. Dietary intervention programs aimed at reducing fat intake have had mixed results in this population. The transtheoretic model is proposed for achieving dietary change. Strategies for changing health behaviors in African-American women include heightening sensitivity to cultural values among health educators and the use of multiple strategies to reinforce messages. To stimulate healthier eating, it is important to incorporate the distinct habitual eating patterns into innovative intervention methods, using effective behavioral change methods. (Am J Obstet Gynecol 1997;176:S255-64.)     

Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates.

High cytoplasmic expression of maspin was described in ovarian cancers of shorter survival rates. Until now, no relationship has been described between expression of maspin and sensitivity to cisplatin in ovarian cancers. This study aimed at examining the relationship between expression of maspin, detected by immunohistochemistry and clinical response to cisplatin in ovarian cancer cases as well as the in vitro sensitivity to cisplatin of 11 ovarian cancer cell lines. The analyzes were performed on 73 samples of ovarian cancer and on A2780P, A2780RCIS, CAOV-3, EFO 21, EFO 27, ES-2, Mdah 2774, OAW 42, OVCAR-3, PA-1, and SKOV-3 ovarian cancer cells. Cytoplasmic maspin expression in studied cells significantly correlated with cisplatin sensitivity. A significantly shorter overall survival and progression-free survival was associated with lower cytoplasmic maspin expression at first-look laparotomies and nuclear maspin expression and secondary cytoreductions. Higher nuclear maspin at first-look laparotomies expression was specific for cases of complete response. In the study, the elevated expression of maspin was shown to be typical for cisplatin-sensitive ovarian cancers.     

High-harmonic spectroscopy of quantum phase transitions in a high-Tc superconductor

We report on the nonlinear optical signatures of quantum phase transitions in the high-temperature superconductor YBCO, observed through high harmonic generation. While the linear optical response of the material is largely unchanged when cooling across the phase transitions, the nonlinear optical response sensitively imprints two critical points, one at the critical temperature of the cuprate with the exponential growth of the surface harmonic yield in the superconducting phase and another critical point, which marks the transition from strange metal to pseudogap phase. To reveal the underlying microscopic quantum dynamics, a strong-field quasi-Hubbard model was developed, which describes the measured optical response dependent on the formation of Cooper pairs. Further, the theory provides insight into the carrier scattering dynamics and allows us to differentiate between the superconducting, pseudogap, and strange metal phases. The direct connection between nonlinear optical response and microscopic dynamics provides a powerful methodology to study quantum phase transitions in correlated materials. Further implications are light wave control over intricate quantum phases, light–matter hybrids, and application for optical quantum computing.

Attosecond technology (1), specifically the process of high harmonic generation (HHG) (2–4), provides an all-optical probe of the microscopic dynamics of atoms, molecules, and solids. Shortly after the first observation of high harmonics in atoms, their generation was understood (4–6) as arising from electron recollision after strong field photoionization and excursion in the continuum. Since the harmonic signal strongly depends on the electron recollision angle and time, high-harmonic spectroscopy (HHS) is a sensitive nonlinear probe of microscopic electronic structure with atomic spatial and suboptical cycle temporal resolution. HHS of solids (7, 8), two-dimensional materials (9, 10), or nanostructured media (11, 12) differs from the gas phase since the optical field–driven electronic wave packet is delocalized over many lattice sites, the wave function depends on the lattice momentum, and a hole has to match the electron’s momentum for recombination to occur (13, 14). Recent experimental efforts extended HHS as nonperturbative probe to quantum materials (9, 10, 15, 16) and to topological insulators (17–19). There have also been several theoretical advances, which suggest using strong fields to probe the physics of Mott insulators (20, 21), alongside the possibility of optically modifying strongly correlated matter (22) and tracking optically induced phase transitions (23), with a recent experiment reported in ref. 24.The sensitivity of HHS to the intricate microscopic details of carriers and lattice predestines HHS to investigate strong interactions and quantum correlations which lead to fascinating new states of matter such as superconductivity. The phase transition into a strongly correlated superconductive state is described by the spontaneous symmetry breaking of the U(1) redundancy when cooling below the critical temperature Tc of the material. As we will show, HHS is a sensitive probe of the dynamic evolution of the superconducting phase transition since the formation of composite bosons by pairing two fermionic spin-1/2 particles (Cooper pairs) changes the distribution of charge carriers, and this sensitively registers in the high harmonic amplitudes and spectral distribution. Pictorially, this is described in SI Appendix, Fig. S1, by a three-step model, consisting of 1) interband excitation process, 2) intraband acceleration, and 3) interband recombination. Pairing below T_c splits the bands by opening a superconducting gap Δ, and in the strongly correlated phase, the three processes of harmonic generation occur within the effective band structure for the Cooper pairs. We will also show that HHS can identify additional phase transitions between quantum phases in the strongly correlated material which are not accessible through the linear optical response, and they are difficult to detect with established methods such as superconducting quantum interference device (SQUID) magnetometry or four-probe transport measurements.A conventional superconductor can be described by the Anderson–Higgs mechanism, which explains that an optical nonlinear response is due to a gapless phase mode (Nambu–Goldstein) and a gapped amplitude mode (Higgs) of the ordering parameter. In the simplest case, and depending on the strength and type of excitation, Boltzmann and Ginzburg–Landau theories (25, 26) predict a second-order response, which mixes with the excitation mode (27, 28), thus the generation of the third harmonic (29). Unconventional high-Tc superconductors are of tremendous interest for a wide range of applications ranging from electronic devices and information processing devices to optical quantum computers and quantum simulators. However, due to their rich landscape of quantum phases and the difficulties of experimental methods to probe the microscopic dynamics, our understanding is still very limited.Among the well-established methods, e.g., transport measurements (30) or magnetic torque measurements (31, 32), photoemission measurements such as angle-resolved photoemission spectroscopy (ARPES) (33, 34) provide direct access to a material’s microscopic carrier distribution and dynamics. The interpretation of such ARPES measurement is, however, complicated by the interpretation of the bulk spectral function and the assumption of independent electron emission despite measuring a strongly correlated electronic state of matter. These are central questions to access the nature of the multibody state, which call for further developments and powerful new tools to aid in the interpretation of the physical mechanism.Therefore, the development of all-optical and ultrafast probes of the macroscopic dynamics inside such materials, which is compatible with existing methods, is highly desirable. To this aim, we apply HHS to investigate the transition between the different phases of the unconventional high-Tc superconductor YBa₂Cu₃O7−d (YBCO). We elucidate the connection between the measured optical spectra, the transition between strange metal and pseudogap phases, and the superconducting phase transition with a strong-field Hubbard model. The HHS measurement clearly shows a departure from the normal conducting phase with an increased formation of Cooper pairs upon cooling. The variation in harmonic orders is linked to phenomenological energy and phase relaxation times, which identify the transition to the fluctuation regime (35, 36), i.e., between the strange metal and pseudogap phases, and the sudden transition at Tc into the superconducting phase. Unconventional superconductors, like YBCO, are material systems in which the formation of composite bosons out of paired fermions is mediated not by phonon exchange but by some other kind of energy exchange (37), for instance, due to spin fluctuations. Such systems present many standing fascinating questions. It is thus important to have new powerful experimental techniques like HHS that provide a fresh and alternate view of the problem.