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•Antibiotic fluoroquinolones are ideal anticancer drug repositioning candidate.•Fluoroquinolones induce cell cycle arrest, apoptosis, modulate EMT and cancer ...stemness.•Fluoroquinolones stimulates cancer specific microRNA biogenesis.•Metal ion complexes of fluoroquinolones possess enhanced anticancer activity.•Derivatives and salt complexes of fluoroquinolones are highly effective anticancer molecules than parent molecule.
Increasing development costs and higher failure rate in clinical trials has reduced the repertoire of newer drugs in the market for clinical use. The most appropriate approach to end the search for newer drugs is “Repositioning”, as it requires less time and money to explore new indication of existing drug or failed drug. In the past, several drugs have been repositioned for different indication but the full potential remains unharnessed. With rise in cancer prevalence and treatment costs, it is imperative to search for newer drugs and the use of repositioning approach may help us. Fluoroquinolones has been used as antibiotics for over four decades now, but recent research highlighted their use as pharmacological compounds with multifaceted implication. Repositioning of fluoroquinolones into anti-cancer molecule seems to be a highly plausible option owing to their profound immunomodulatory, pro-apoptotic, anti-proliferative and anti-metastatic potential. The present review provides a comprehensive account of the recent and past explorations pertaining to the anti-cancer activity of fluoroquinolones and also discusses the various approaches that are being considered to remodel them for the treatment of cancer.
Extensive usage of antibiotics has created an unprecedented scenario of the rapid emergence of many drug-resistant bacteria, which has become an alarming public health concern around the globe. ...Search for better alternatives that are as efficacious as antibiotics led to the discovery of antimicrobial peptides (AMPs). These small cationic amphiphilic peptides have emerged as a promising option as antimicrobial agents, owing to their multifaceted implications against varied pathogens. Recent years have witnessed tremendous growth in research on AMPs resulting in them being tested in clinical trials of which six got approved for topical application. The relatively less successful outcome has been attributed to the poor cell selectivity shown by most of the naturally occurring AMPs. This drawback needs to be circumvented by identifying strategies to design safe and effective peptides. In the present review, we have emphasized the importance of heptad repeat sequence (leucine and/or phenylalanine zipper motif) as a tool that has shown great promise in remodeling the toxic AMPs to safe antimicrobial agents.
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•Heptad Repeat Sequence, an efficient tool for designing cell-selective peptides.•Heptad Repeats comprises repetitive pattern of seven amino acids in a coiled coil structure.•Leucine and Phenylalanine Zipper Motifs are key structural elements of Heptad Repeats.•Heptad Repeat Sequence is a model system for designing short and synthetic peptides.
A
bstract
A (semiclassical) holographic computation of the deconfinement temperature at
intermediate coupling
from (a top-down)
ℳ
-theory dual of thermal QCD-like theories, has been missing in the ...literature. In the process of filling this gap, we demonstrate a novel UV-IR connection, (conjecture and provide evidence for) a non-renormalization beyond one loop of
ℳ
-
c
hiral perturbation theory
1
-compatible deconfinement
T
emperature, and show equivalence with an
E
ntanglement (as well as Wald) entropy
2
computation, up to terms
Q
uartic in curvature (
R
). We demonstrate a
F
lavor-
M
emory (FM) effect in the
ℳ
-theory uplifts of the gravity duals, wherein the no-braner
ℳ
-theory uplift retains the “memory” of the flavor
D
7-branes of the parent type IIB dual in the sense that a specific combination of the aforementioned quartic corrections to the metric components precisely along the compact part (given by
S
3
as an
S
1
-fibration over the vanishing two-cycle
S
2
) of the non-compact four-cycle “wrapped” by the flavor
D
7-branes, is what determines, e.g., the Einstein-Hilbert action at O(
R
4
). The aforementioned linear combination of 𝒪(
R
4
) corrections to the
ℳ
-theory uplift
3
,
4
metric, upon matching the holographic result from
ℳχ
PT
1
with the phenomenological value of the coupling constant of one of the SU(3) NLO
χ
PT Lagrangian of
5
, is required to have a definite sign. Interestingly, in the decompactification (or “
M
KK
→ 0”) limit of the spatial circle in
1
to recover a QCD-like theory in four dimensions after integrating out the compact directions, we not only derive this, but in fact obtain the values of the relevant 𝒪(
R
4
) metric corrections. Further, equivalence with Wald entropy for the black hole in the high-temperature
ℳ
-theory dual at 𝒪(
R
4
) imposes a linear constraint on a similar linear combination of the abovementioned metric corrections. Remarkably, when evaluating the deconfinement temperature from an entanglement entropy computation in the thermal gravity dual, due to a delicate cancellation between the contributions arising from the metric corrections at 𝒪(
R
4
) in the
ℳ
theory uplift along the
S
1
-fiber and an
S
2
(which too involves a similar
S
1
-fibration) resulting in a non-zero contribution only along the vanishing
S
2
surviving, one sees that there are consequently no corrections to
T
c
at quartic order in the curvature supporting the conjecture made on the basis of a semiclassical computation.
Some remarkable animal species require an opposite-sex partner for their sexual development but discard the partner's genome before gamete formation, generating hemi-clonal progeny in a process ...called hybridogenesis. Here, we discovered a similar phenomenon, termed pseudosexual reproduction, in a basidiomycete human fungal pathogen, Cryptococcus neoformans, where exclusive uniparental inheritance of nuclear genetic material was observed during bisexual reproduction. Analysis of strains expressing fluorescent reporter proteins revealed instances where only one of the parental nuclei was present in the terminal sporulating basidium. Whole-genome sequencing revealed that the nuclear genome of the progeny was identical with one or the other parental genome. Pseudosexual reproduction was also detected in natural isolate crosses where it resulted in mainly MATalpha progeny, a bias observed in Cryptococcus ecological distribution as well. The mitochondria in these progeny were inherited from the MATa parent, resulting in nuclear-mitochondrial genome exchange. The meiotic recombinase Dmc1 was found to be critical for pseudosexual reproduction. These findings reveal a novel, and potentially ecologically significant, mode of eukaryotic microbial reproduction that shares features with hybridogenesis in animals.
A
bstract
Using the pull-back of the perturbed type IIA metric corresponding to the perturbation of
1
’s M-theory uplift of
2
’s UV-complete top-down type IIB holographic dual of large-
N
thermal ...QCD, at finite coupling, we obtain the interaction Lagrangian corresponding to exotic scalar glueball(
G
E
)-
ρ/π
-meson interaction, linear in the exotic scalar glueball and up to quartic order in the π mesons. In the Lagrangian the coupling constants are determined as (radial integrals of)
1
’s M-theory uplift’s metric components and six radial functions appearing in the M-theory metric perturbations. Assuming
M
G
>
2
M
ρ
, we then compute
ρ
→ 2
π, G
E
→ 2
π,
2
ρ, ρ
+ 2
π
decay widths as well as the direct and indirect (mediated via ρ mesons)
G
E
→ 4
π
decays. For numerics, we choose
f
01710 and compare with previous calculations. We emphasize that our results can be made to match PDG data (and improvements thereof) exactly by appropriate tuning of some constants of integration appearing in the solution of the M-theory metric perturbations and the
ρ
and
π
meson radial profile functions — a flexibility that our calculations permits.
The continuous emergence of antifungal drug resistance is a mounting concern for the treatment of fungal infections worldwide. While many pathogenic fungi exhibit some level of antifungal drug ...resistance, the identification of Candida auris has brought this phenomenon to the fore in recent years. C. auris exhibits resistance to all antifungal drugs used for treatment, and it does so at a very high rate, with more than 90% of isolates being resistant to at least one drug and roughly 4% being panresistant. However, the environmental factors driving this exceptionally high antifungal drug resistance remain unidentified. The presence of C. auris on stored apples that are treated with antifungals during storage suggests a possible route to selection of drug-resistant C. auris isolates that may have contributed to the evolution of this deadly pathogen. This study further suggests that the adage "an apple a day keeps the doctor away" may need to be revisited in light of the discovery of C. auris on the surface of apples.
A
bstract
Obtaining the values of the coupling constants of the low energy effective theory corresponding to QCD, compatible with experimental data, even in the (vector) mesonic sector from (the
M
...-theory uplift of) a UV-complete string theory dual, has thus far been missing in the literature. We take the first step in this direction by obtaining the values of the coupling constants of the
O
(
p
4
)
χ
PT Lagrangian in the chiral limit involving the NGBs and
ρ
meson (and its flavor partners) from the
M
-theory/type IIA dual of large-
N
thermal QCD, inclusive of the
O
(
R
4
) corrections. We observe that ensuring compatibility with phenomenological/lattice results (the values) as given in
1
, requires a relationship relating the
O
(
R
4
) corrections and large-
N
suppression. In other words, QCD demands that the higher derivative corrections and the large-
N
suppressed corrections in its M/string theory dual, are related. As a bonus, we explicitly show that the
O
(
R
4
) corrections in the UV to the
M
-theory uplift of the type IIB dual of large-
N
thermal QCD at low temperatures, can be consistently set to be vanishingly small.
There is lack of information on the magnitude of depression among elderly population in India. This systematic review and meta-analysis aimed to estimate the prevalence of depression among elderly ...population in India.
PubMed, Scopus, Web of Science, Embase, PsycINFO, IndMed, and Google Scholar were searched to identify articles reported community-based prevalence of depression among elderly population using screening tools. This study included the articles published during the years 1997 to 2016. Studies conducted in the special population groups, hospitals, reported only a subcategory of depression, and not specified the screening tool were excluded. Data were extracted from published reports and any missing information was requested from authors. Estimates were pooled using random-effects meta-analyses. Subgroup and sensitivity analysis were performed. The publication bias was evaluated by using Egger's test and visual inspection of the symmetry in funnel plots.
Fifty-one studies from 16 States of India were included as 56 datasets, which estimated the prevalence of depression among Indian elderly population as 34.4% (95% CI: 29.3-39.7). In sub-group analysis, the pooled prevalence was higher among females, rural populations, and in the eastern part of the country. Studies using non-probability sampling, and GDS and CES-D screening tool showed higher prevalence. Exclusion of the studies with sample size less than 100 and low-quality studies (score < 5/8) had no effect on the estimate of the prevalence. The studies that excluded dementia before assessment of depression had lower prevalence.
About one third elderly population of India suffered from depression with female preponderance. The estimates varied with type of study tool, geographic region, sampling methods, and presence of dementia. The pooled estimate should be interpreted with caution as the studies included in this review had varied methodological approach and screening tools.
DNA strand consisting of multiple runs of guanines can adopt the non-canonical, four-stranded DNA secondary structure known as G-quadruplex or G4 DNA. G4 DNA is thought to play an important role in ...transcriptional and translational regulation of genes, DNA replication, genome stability, and oncogene expression in eukaryotic genomes. In other organisms including several bacterial pathogens and some plant species, the biological role of G4 DNA and G4 RNA is starting to be explored. Recent investigation showed that G4 DNA and G4 RNA are generally conserved across plant species.
analyses of several bacterial genomes identified the putative guanine-rich, G4 DNA-forming sequences in the promoter regions. They were particularly abundant in certain gene classes, suggesting that these highly diverse structures can be employed to regulate expression of genes involved in secondary metabolite synthesis and signal transduction. Furthermore, in the pathogen
, the distribution of G4 motifs and their potential role in the regulation of gene transcription advocate for the use of G4 ligands to develop novel antitubercular therapies. In this review, we discuss the various roles of G4 structures in bacterial DNA and the application of G4 DNA as an inhibitor or therapeutic agent to tackle the bacterial pathogens.
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